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T Back

Publications and source records attributed to T Back.

At least 37 records · Page 2Linked to original sources
PubMed1997

Noninvasive near infrared spectroscopy monitoring of regional cerebral blood oxygenation changes during peri-infarct depolarizations in focal cerebral ischemia in the rat.

Intermittent peri-infarct depolarizations (PID), which spread from the vicinity of the infarction over the cortex, have been reported in focal ischemia. These depolarizations resemble cortical spreading depression except that they damage the cortex and enlarge the infarct volume possibly because of compromised oxygen delivery. The main purpose of this study was to evaluate the noninvasive technique of near-infrared spectroscopy (NIRS) for the identification of PID and to evaluate its capability for further pathophysiological studies. We used male barbiturate-anesthetized Wistar rats (n = 10) in which middle cerebral artery occlusion had been performed with a surgical thread. Middle cerebral artery occlusion resulted in a drop in parietally measured regional cerebral blood flow (laser Doppler flowmetry) to 31 +/- 8% of baseline flow. Six +/- 4 minutes after the induction of focal ischemia, 5 +/- 2 direct current deflections were recorded during a one-hour measurement period which may be regarded as PID. Measuring regional cerebral blood oxygenation changes with a NIRO 500 revealed dynamic concentration changes in the three chromophores oxyhemoglobin [HbO2], deoxyhemoglobin [Hb], and the oxidized form of cytochrome aa3 [CytO] during PID. Typically, an initial slight decrease of [HbO2] (-6.1 +/- 1.7 arbitrary units [AU] and an increase of [Hb] (+11.5 +/- 7.7 AU) were followed by an increase of [HbO2] (+10.8 +/- 4.7 AU) and a decrease of [Hb] (-4.7 +/- 5.5 AU); [CytO] decreased during the depolarizations (-2.0 +/- 1.2 AU). We conclude that NIRS can detect typical PID-associated changes in blood oxygenation. We hypothesize that during the course of PID, unlike "normal" spreading depression, hypoxygenation precedes hyperoxygenation of the microcirculation in a given cortex volume as the depolarization wave propagates through hemodynamically compromised to intact tissue. This would accord with the known damaging effect of PID. The NIRS "fingerprint" of PID encourages the search for PID during early stroke in patients.

Animals↗
PubMed1996

Monitoring the temporal and spatial activation pattern of astrocytes in focal cerebral ischemia using in situ hybridization to GFAP mRNA: comparison with sgp-2 and hsp70 mRNA and the effect of glutamate receptor antagonists.

We investigated the temporo-spatial expression of astrocyte glial fibrillary acidic protein (gfap) and sulfated glycoprotein 2 (sgp-2) mRNAs in comparison to 70-kDa heat shock protein (hsp70) mRNA by in situ hybridisation in rats subjected to permanent occlusion of the middle cerebral artery (MCA). Gfap mRNA started to increase in the cingulate cortex of the lesioned hemisphere 6 h after MCA occlusion and gradually spread over the lateral part of the ipsilateral cortex and the striatum from 12 h to 3 days, peaking at 3 days after MCA occlusion. Gfap mRNA also increased in the contralateral cingulate cortex and corpus callosum at 12 and 24 h. Hsp70 mRNA increased markedly in the ipsilateral cortex adjacent to the ischemic lesion, and slightly within the lesion area from 3 to 24 h and disappeared after 3 days. By 7 days, gfap and sgp-2 mRNAs were increased markedly in the peri-infarct area, and in the ipsilateral thalamus parallel with the delayed neuronal damage, whereas the widespread increase of gfap mRNA in the ipsilateral hemisphere declined. Post-occlusion treatment with the glutamate receptor antagonists MK-801 and NBQX slightly attenuate the induction of gfap but did not qualitatively affect the topical expression pattern. Within the cingulate cortex MK-801 treatment resulted in a significant decrease of the signal intensity at all survival times, reflecting most likely an attenuation of lesion-induced spreading depression like depolarization waves by MK-801. The area of hsp70 expression was reduced by both MK-801 and NBQX, most likely reflecting the decrease of the lesion area by both treatment regimens. Our study thus revealed an early and widespread increase of gfap mRNA in the non-ischemic area including the contralateral hemisphere starting between 3 and 6 h, and a delayed circumscribed expression in the peri-infarct border zone after 1 week. Comparison with the expression of hsp70 mRNA suggests that the absence of an early gfap mRNA induction in the peri-lesion zone reflects an impairment of astrocytic function which may be of importance for infarct growth during the early evolution of the pathological process.

Animals↗
PubMed1996

Neurobehavioral consequences of induced spreading depression following photothrombotic middle cerebral artery occlusion.

In a model of experimental focal cerebral ischemia, we have recently reported a strong correlation between the magnitude of ischemic depolarizations in the peri-infarct borderzone and the extent of histological injury. In the present study, we assessed the neurobehavioral consequences of spontaneously occurring and induced ischemic depolarizations in rats following middle cerebral artery (MCA) occlusion, as well as the effects of induced spreading depression (SD) in intact animals. Halothane-anesthetized, artificially ventilated Sprague-Dawley rats underwent photothrombotic MCA occlusion coupled with ipsilateral common carotid artery (CCA) occlusion. The electroencephalogram and direct current (DC) potential were recorded in the parietal infarct borderzone-corresponding to the cortical forelimb area-for 3 h following MCA occlusion. Group 1 rats (n = 9) received MCA/CCA occlusion, and the spontaneously occurring negative DC shifts were recorded in the ischemic borderzone. In Group 2 animals (n = 9), the (non-ischemic) frontal pole of the ipsilateral hemisphere was electrically stimulated in order to double the frequency of peri-infarct DC shifts occurring over the initial 3 h postocclusion. Group 3 consisted of intact rats (n = 3) in which SD was repeatedly evoked in the frontal pole. Four animals served as sham-operated controls. A battery of sensorimotor behavioral tests, consisting of beam balance, postural reflex and elicited forelimb placing, was applied in a blinded fashion. Sham controls and animals of Groups 1 and 2 were tested 24 h after surgery, and Group 3 rats were tested 2, 6 and 24 h after generation of SDs. A cumulative neurobehavioral index, ranging from 0 to 144, was calculated by adding the individual test results. Brains were perfusion-fixed 24 h following surgery for calculation of volumes of infarction and scattered neuronal injury. Functional outcome at 24 h was significantly worse in Group 2 animals (spontaneous plus induced ischemic depolarizations) (neurobehavior index 43 +/- 19, mean +/- S.D.) compared to Group 1 rats, in which only spontaneous depolarizations occurred (neurobehavior index 24 +/- 19, P < 0.05). The cumulative neurobehavioral index of Group 1 and 2 animals correlated positively with the volume of total ischemic injury (r = 0.765, P < 0.001) and with the frequency of ischemic depolarizations (r = 0.474, P < 0.05). Correlations between severe forelimb placing deficits and severe degrees of histological injury (necrosis or ischemic cell change) in the corresponding primary sensorimotor cortical region FR1 were significant in these rats. Group 3 rats showed severe neurobehavioral deficits at 2 and 6 h following SD stimulation (index 57 +/- 1 and 39 +/- 1, respectively) but returned to normal at 24 h (4 +/- 0). The findings indicate that cortical spreading depression is accompanied by transient neurobehavioral deterioration and that SD in the ischemic hemisphere of animals subjected to MCA occlusion worsened functional outcome 24 h after surgery.

Animals↗
PubMed1996

Three-dimensional metabolic and hemodynamic imaging of the normal and ischemic rat brain.

Unique insights into the topography of local metabolism/blood flow interrelationships in focal cerebral ischemia have afforded by the recent development of powerful image-processing techniques permitting three-dimensional (3D) autoradiographic image-averaging and analysis of replicate studies by a novel method termed "disparity analysis". This method, based upon a linear affine transformation model, directly estimates scaling, translation and rotation parameters simultaneously. The method was validated in awake Wister rats studied for local cerebral glucose metabolism (lCMRgl) with 14C-2-deoxyglucose. Brains were subserially sectioned, aligned by disparity analysis, and mapped into a common template so as to generate aggregate 3D data sets of the mean and standard deviation of the entire series (n = 9). Internal anatomic architecture was faithfully represented in the average image, and Fourier analysis revealed satisfactory retention of low-frequency information. The method was then applied to study metabolism/blood flow relationships in the acute focal ischemic penumbra of Sprague-Dawley rats subjected to distal photothrombotic middle cerebral artery (MCA) occlusion, coupled with permanent ipsilateral and 1 h contralateral common carotid artery occlusions. Matched series were studied for lCBF at 1.5 h and for lCMRgl at 1.25-2 h post-occlusion. The averaged lCBF image revealed the ischemic penumbra (defined as lCBF 20-40% of control) to form a "shell" around the cortical ischemic core and a confluent aggregate at the anterior and posterior poles of the core-zone. lCMRgl in the penumbra was heterogeneous, ranging from near-normal to markedly increased. An average lCMRgl/lCBF ratio data set revealed marked metabolism-flow uncoupling in penumbral pixels, averaging nearly five-fold above control ratio values. Sustained deflections of the DC potential were recorded in the penumbra, the site of marked uncoupling. This analysis defined for the first time the 3D topography of the ischemic penumbra and substantiated marked metabolism/flow dissociation, which is believed to be a metabolic consequence of the energy demand imposed by repeated peri-infarct depolarizations.

Animals↗
PubMed1996

Induction of spreading depression in the ischemic hemisphere following experimental middle cerebral artery occlusion: effect on infarct morphology.

This study was undertaken to test whether transient depolarizations occurring in periinfarct regions are important in contributing to infarct spread and maturation. Following middle cerebral artery (MCA) occlusion we stimulated the ischemic penumbra with recurrent waves of spreading depression (SD) and correlated the histopathological changes with the electrophysiological recordings. Halothane-anesthetized, artificially ventilated Sprague-Dawley rats underwent repetitive stimulation of SD in intact brain (Group 1; n = 8) or photothrombotic MCA occlusion coupled with ipsilateral common carotid artery occlusion (Groups 2 and 3, n = 9 each). The electroencephalogram and direct current (DC) potential were recorded for 3 h in the parietal cortex, which represented the periinffarct border zone in ischemic rats. In Group 2, only spontaneously occurring negative DC shifts occurred; in Group 3, the (nonischemic) frontal pole of the ischemic hemisphere was electrically stimulated to increase the frequency of periinfarct DC shifts. Animals underwent perfusion-fixation 24 h later, and volumes of complete infarction and scattered neuronal injury ("incomplete infarction") were assessed on stained coronal sections by quantitative planimetry. Electrical induction of SD in Group 1 did not cause morphological injury. During the initial 3 h following MCA occlusion, the number of spontaneous periinfarct depolarization in Group 2 (7.0 +/- 1.5 DC shifts) was doubled in Group 3 by frontal current application (13.4 +/- 2.7 DC shifts; p < 0.001). The duration as well as the integrated negative amplitude of DC shifts over time were significantly greater in Group 3 than in Group 2 rats (duration, 5.7 +/- 3.8 vs. 4.1 +/- 2.5 min; p < 0.05). Histopathological examination disclosed well-defined areas of pannecrosis surrounded by a cortical rim exhibiting selectively damaged acidophilic neurons and astrocytic swelling in otherwise normal-appearing brain. Induction of SD in the ischemic hemisphere led to a significant increase in the volume of incomplete infarction (19.0 +/- 6.1 mm3 in Group 3 vs. 10.3 +/- 5.1 mm3 in Group 2; p < 0.01) and of total ischemic injury (100.7 +/- 41.0 mm3 in Group 3 vs. 66.5 +/- 24.7 mm3 in Group 2; p < 0.05). The integrated magnitude of DC negativity per experiment correlated significantly with the volume of total ischemic injury (r = 0.780, p < 0.0001). Thus, induction of SD in the ischemic hemisphere accentuated the development of scattered neuronal injury and increased the volume of total ischemic injury. This observation may be explained by the fact that with limited perfusion reserve, periinfarct depolarization are associated with episodic energy failure in the acute ischemic penumbra.

Animals↗
PubMed1996

Systemic nitric oxide synthase inhibition does not affect brain oxygenation during cortical spreading depression in rats: a noninvasive near-infrared spectroscopy and laser-Doppler flowmetry study.

Cortical spreading depression (CSD) has been implicated in the migraine aura and in stroke. This study demonstrates near-infrared spectroscopy (NIRS) for the first time as capable of noninvasive on-line detection of CSD in the pentobarbital-anesthetized rat. CSD was accompanied by a brief and rapid increase of regional CBF (by laser-Doppler flowmetry) to 200-400% baseline. NIRS demonstrates that this hyperperfusion is associated with concentration increases of oxyhemoglobin, while deoxyhemoglobin decreases. Simultaneously, oxygen partial pressure, measured on the brain surface with a solid-state polarographic probe, was shown to be raised by at least 14 mm Hg during CSD. Oxygen-dependent phosphorescence life-time quenching measurements confirmed this finding. NIRS data on cytochrome aa3, however, showed a CSD-related shift toward a more reduced state, despite raised blood oxygenation. This may suggest either limited O2 transport from the blood to mitochondria or decreased oxygen utilization during CSD as supposed by theories about compartmentalization of energy metabolism favoring glycolytic rather than aerobic energy supply during CSD. However, the data on cytochrome aa3 warrant caution and are discussed critically. Nitric oxide synthase inhibition by systemic application of N'-nitro-L-arginine had no significant effect on the perfusion response or the tissue PO2 during CSD. During most CSD episodes, a brief decrease in MABP by 4-8 mm Hg was noted that might be caused by functional decortication during CSD.

Animals↗
PubMed1995

Changes of relaxation times (T1, T2) and apparent diffusion coefficient after permanent middle cerebral artery occlusion in the rat: temporal evolution, regional extent, and comparison with histology.

The quantitative NMR parameters T1, T2, rho, and apparent diffusion coefficient (ADC) were determined during the 7 h after middle cerebral artery occlusion in rats. In the normal caudate-putamen (CP), 869 +/- 145 ms and 72 +/- 2 ms for T1 and for T2, respectively, were found; the corresponding values for cortex were 928 +/- 117 ms and 73 +/- 2 ms. The ADC showed significant dependence on gradient direction: diffusion along x resulted in 534 +/- 53 microns 2/s (CP) and 554 +/- 62 microns 2/s (cortex), and along y in 697 +/- 58 microns 2/s (CP) and 675 +/- 53 microns 2/s (cortex). In the ischemic territory, a continuous increase over time of both relaxation times was observed in the CP, leading to an increase of 29 +/- 20% (T1) and 51 +/- 41% (T2) above control level. ADC dropped to 63 +/- 15% of control in the CP and to 74 +/- 4% of control in the temporal cortex. No significant change was noted in proton density during the observation period. Strongest ADC reduction was in the center of the ischemic territory (< or = 60% of control) surrounded by a region of lesser reduction (< or = 80% of control). During the early part of the study, the area of reduced ADC was larger than that of elevated relaxation times. Toward the end of the experiment, the area of increased relaxation times approached that of decreased ADC at < or = 80% of control. Good agreement of histological presentation of infarct with the total area of decreased ADC (< or = 80%) was demonstrated.

Animals↗
PubMed1995

Evolution of acute focal cerebral ischaemia in rats observed by localized 1H MRS, diffusion-weighted MRI, and electrophysiological monitoring.

Focal cerebral ischaemia was produced in 11 rats by permanent occlusion of the right middle cerebral artery (MCA) using a suture model modified to enable manipulation with the animals in situ in an NMR spectrometer. The development of the ischaemic insults and the resultant infarcts were observed for up to 6 h by localized 1H MRS and diffusion-weighted MRI while performing continuous monitoring of electroencephalogram and extracellular DC potential. The ischaemic areas were depicted as regions of hyperintensity in the diffusion-weighted images. Signals due to lactate became visible in the 1H spectra after MCA occlusion indicating the onset of anaerobic glycolysis. A depletion of N-acetylaspartate was seen in all animals post-occlusion. Transient or stepwise increases of lactate were observed to occur coincidentally with the events of spontaneous transient peri-infarct depolarization detected by the electrophysiological measurements. Expansion of the ischaemic area delineated in the diffusion-weighted images also accompanied peri-infarct depolarizations. These observations are consistent with transient peri-infarct depolarization playing a role in the growth of infarcts.

Acute Disease↗
PubMed1995

Effect of extracorporeal life support on cerebral blood flow, metabolism and electrophysiology in normothermic cats.

OBJECTIVE: Recently, extracorporeal life support (ECLS) by venoarterial bypass perfusion has been recommended for the treatment of refractory respiratory and/or cardiac failure but the safety of this application for the brain is not yet established. Therefore, the effects of normothermic ECLS on cerebral blood flow, metabolism and electrophysiology were studied in cats with total arrest of cardiopulmonary circulation. DESIGN: An extracorporeal circulation (ECC) system, consisting of a roller pump, a membrane oxygenator and a heat exchanger, was connected to the circulation of cat by cannulae inserted via the jugular vein and femoral vessels. After 2 h ECLS brains were frozen in situ and investigated for changes in regional metabolism. MEASUREMENTS AND RESULTS: During 2 h ECC hematocrit declined from 37 +/- 7% to 21 +/- 10% (means +/- SD, p < 0.05), cerebral blood flow decreased to 73 +/- 14% of control (p < 0.05) and cerebral oxygen delivery to 46 +/- 13% of control (p < 0.05) although arterial blood pressure and bypass flow rate did not change. Plasma lactate increased from 0.8 +/- 0.3 to 9.2 +/- 4.2 mumol/ml (p < 0.05), and brain tissue lactate from 2.3 +/- 0.9 to 10.6 +/- 2.7 mumol/g (p < 0.05). Hematocrit correlated positively with cerebral oxygen delivery (r = 0.86, p < 0.001). CONCLUSIONS: These data demonstrate that ECLS is associated with reduced cerebral oxygen delivery and may cause brain hypoxia despite normal blood pressure. This complication may contribute to the high incidence of neurological disturbances after prolonged ECLS.

Animals↗
PubMed1995

Transient forebrain ischemia induces an immediate-early gene encoding the mitogen-activated protein kinase phosphatase 3CH134 in the adult rat brain.

In fibroblasts, serum stimulation has been shown to activate the immediate-early gene 3CH134 encoding a dual specificity protein phosphatase that regulates mitogen-activated protein kinase. We report here that 3CH134 messenger RNA levels increase during recirculation following 30 min forebrain ischemia in the rat brain. In normal rat brains, 3CH134 messenger RNA was found mainly in neurons of the cortex and thalamus. At recirculation periods up to 1 h after 30 min ischemia, 3CH134 messenger RNA increased in neurons and glial cells of all previously ischemic brain regions. After 3 and 6 h recirculation, a prominent increase of 3CH134 messenger RNA was observed in the pyramidal cell layer of all sectors of the hippocampus and the granule cells of the dentate gyrus, whereas in the other brain regions messenger RNA levels returned to control. Up to 6 h of recirculation the spatial induction pattern of 3CH134 was similar to the pattern observed for the immediate-early genes c-fos and c-jun. Within the hippocampus a similar pattern was also observed for the heat shock protein hsp70 messenger RNA. At 12 and 24 h after ischemia, increased levels of 3CH134 messenger RNA persisted in hippocampal neurons; at the same time a delayed increase of 3CH134 messenger RNA was observed in large neurons of the thalamus and in glial cells in damaged regions of the striatum. At later survival periods, 3CH134 messenger RNA returned to control levels. Our study shows that the mitogen-activated protein kinase phosphatase 3CH134 is induced in the brain after a period of global ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Relationship between diffusion-weighted MR images, cerebral blood flow, and energy state in experimental brain infarction.

The regional evolution of brain infarction was studied in Wistar rats submitted to remotely controlled thread occlusion of the middle cerebral artery. Occlusion was performed in the magnet of an NMR tomography system to allow continuous recording of diffusion-weighted images. After 30 min (n = 6) or 2 h (n = 9), cerebral blood flow was measured by [14C] iodoantipyrine autoradiography while the regional distribution of ATP, glucose, lactate, and pH was imaged using pictorial bioluminescence and fluoroscopic methods. In diffusion-weighted images, the hemispheric lesion area (HLA) at the level of caudate-putamen amounted to 54.2 +/- 10.9% after 30 min and to 67.0 +/- 5.9% after 2 h vascular occlusion. These areas corresponded to the regions exhibiting tissue acidosis (60.8 +/- 9.3% and 70.4 +/- 4.5%), but were clearly larger than those in which ATP was depleted (22.3 +/- 20.8% and 49.6 +/- 12.9% after 30 min and 2 h, respectively). The threshold of blood flow for the increase of signal intensity in diffusion-weighted images increased between 30 min and 2 h occlusion from 34 to 41 ml/100 g per minute, the threshold of acidosis from 40 to 47 ml/100 g per minute, and the threshold for ATP depletion from 13 to 19 ml/100 g per minute. Our study demonstrates that diffusion-weighted imaging detects both the core and the penumbra of the evolving infarction but is not able to differentiate between the two parts. It further shows that the ischemic lesion grows during the initial 2 h of vascular occlusion, and that the size of the infarct core increases more rapidly than that of the penumbra.

Adenosine Triphosphate↗
PubMed1995

A modified rat model of middle cerebral artery thread occlusion under electrophysiological control for magnetic resonance investigations.

Previous magnetic resonance (MR) investigations of middle cerebral artery (MCA) occlusion in rats were limited by the lack of early post-occlusion MR measurements and/or electrophysiological monitoring. Therefore, we have developed a technique which allows to perform MCA occlusion inside the magnet under simultaneous recording of EEG and direct current (DC) potentials for monitoring the ischemic insult. Rats underwent intraluminal thread occlusion of the right MCA inside the MR tomograph via a catheter extension device, while EEG and DC potentials were recorded by non-magnetic graphite electrodes. The thread was slowly advanced until electrophysiological changes appeared. Diffusion-weighted MR images (DWI) were obtained before and repeatedly after MCA occlusion for up to 7 h. Thereafter, rat brains were frozen in situ or fixed by transcardiac perfusion and investigated by biochemical and histological techniques. In 15 of 18 animals (83%), MCA thread insertion caused immediate EEG changes and a negative DC potential shift at 4.4 +/- 1.8 min (mean +/- SD) after occlusion. In all animals with electrophysiological changes, signal intensity of DWI began to increase within the MCA territory at 12-14 min post-occlusion (the end of the first measurement), and continued to rise throughout the observation period. Ischemia was confirmed by demonstrating focal areas of energy depletion on ATP images. In the animals without electrophysiological changes, DWI or biochemical alterations were absent or confined to the central part of caudate-putamen. The histological lesion area of successfully occluded animals amounted to 70.1 +/- 5.8% of the ipsilateral hemisphere at the level of caudate-putamen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1995

Three-dimensional image analysis of brain glucose metabolism-blood flow uncoupling and its electrophysiological correlates in the acute ischemic penumbra following middle cerebral artery occlusion.

The relationship between local cerebral glucose utilization (LCMRglc) and local CBF (LCBF) is known to be disturbed in regions surrounding an acute focal ischemic lesion--areas that undergo repeated transient depolarizations. In this study, we evaluated the relationship between LCMRglc and LCBF in the acute focal ischemic penumbra to quantify metabolism-flow uncoupling, and we related these findings to local electrophysiological measurements. A novel strategy utilizing three-dimensional (3D) autoradiographic image averaging yielded group 3D reconstructions of LCBF, LCMRglc, and the CMR/CBF ratio. The distal right middle cerebral artery of Sprague-Dawley rats was occluded by laser-driven photothrombosis following administration of the photosensitizing dye rose bengal; this was coupled with permanent ipsilateral and 1-h contralateral common carotid artery occlusions. LCBF (n = 7) and LCMRglc (n = 7) were measured autoradiographically at 1.25 and 1.5-2 h postocclusion, respectively, in matched animal groups. Within the ischemic penumbra (defined as having LCBF of 20-40% of control or 0.23-0.47 ml g-1 min-1), LCMRglc showed a heterogeneous pattern with values ranging from near normal to markedly increased. The resulting CMRglc/CBF ratio in this zone was 234 +/- 100 mumol/100 ml (mean +/- SD), representing a severe degree of metabolism-flow dissociation when compared with the CMRglc/CBF ratio of 51.0 +/- 28.7 mumol/100 ml of the contralateral (normal) hemisphere. Metabolism-flow uncoupling was confined to the ipsilateral cortex and was most prominent at the anterior and posterior coronal poles of the ischemic lesion. In the frontoparietal penumbra, where marked uncoupling was observed, sustained deflections of the DC potential were recorded, which increased significantly in duration over the initial 65 min postocclusion. Both the heterogeneous pattern of LCMRglc and the widespread distribution of increased CMRglc/CBF ratio in the ischemic penumbra are thought to reflect the metabolic consequences of periinfarct depolarizations. Analysis of averaged 3D autoradiographic data sets provides a powerful means for assessing metabolism-flow uncoupling surrounding an ischemic focus.

Animals↗
PubMed1994

Transient cell depolarization after permanent middle cerebral artery occlusion: an observation by diffusion-weighted MRI and localized 1H-MRS.

Focal cerebral ischemia causes rapid intensity changes in diffusion-weighted images (DWI) and elevated lactate as detected by localized proton spectroscopy (1H-MRS). To investigate whether such changes can also be evoked by perischemic depolarizations, we combined DWI and 1H-MRS measurements with DC potential recordings. About 40 min after occlusion of the middle cerebral artery in a rat, a negative DC deflection was observed indicating transient cell depolarization. Coincidentally with the depolarization a transient increase of the DWI signal intensity and a partially reversible increase of lactate occurred in the periphery of the ischemic territory. These results show that peri-ischemic depolarization, known to contribute to the evolution of cerebral infarction, evokes disturbances that can be detected by DWI and 1H-MRS.

Animals↗
PubMed1994

Differential expression of the immediate early genes c-fos, c-jun, junB, and NGFI-B in the rat brain following transient forebrain ischemia.

The temporospatial expression pattern of four immediate early genes (IEGs) (c-fos, c-jun, junB, NGFI-B) following 30 min of global ischemia was investigated in rat brains by in situ hybridization and immunohistochemistry (c-fos). All examined IEG mRNAs, as well as Fos-like immunoreactivity, increased transiently in vulnerable and resistant brain regions following ischemia, but the induction profiles were distinct. Ischemia caused a post-ischemic early-onset, transient c-fos induction in wide-spread regions, as well as a late-onset induction restricted to vulnerable regions. Late-onset c-fos induction was observed in the CA1 region and the ventral thalamus but not in the striatum or neocortex, where neurons degenerate at a quicker pace. After recirculation, c-jun mRNA appeared to be initially coinduced with c-fos mRNA, but c-jun mRNA levels remained elevated or increased in various regions, including all vulnerable regions, when c-fos mRNA had already declined to near basal levels. Compared to c-fos and c-jun, junB induction was less pronounced and confined largely to the dentate gyrus. NGFI-B mRNA increased moderately and only in brain regions exhibiting the most dramatic c-fos increases and with similar kinetics. The differential activation of the investigated IEGs suggests that rather complex long-term adaptive processes may be initiated at the genomic level after global ischemia. The present findings provide further evidence that the activation of IEGs forms part of the brain's metabolic response to ischemia, but no simple correlation appears to exist between the induction of the investigated IEGs and the phenomenon of selective vulnerability.

Animals↗
PubMed1994

Cortical negative DC deflections following middle cerebral artery occlusion and KCl-induced spreading depression: effect on blood flow, tissue oxygenation, and electroencephalogram.

In the periphery of ischemic brain lesions, transient spreading depression-like direct current (DC) deflections occur that may be of pathophysiological importance for determining the volume of the ischemic infarct. The effect of these deflections on cerebral blood flow, tissue oxygen tension, and electrophysiology was studied in rats submitted to intraluminal thread occlusion of the middle cerebral artery (MCA) and compared with the changes following potassium chloride (KCl)-induced spreading depression of intact animals. Immediately after MCA occlusion, cortical laser-Doppler flow (LDF) in the periphery of the MCA territory sharply decreased to 35 +/- 14% of control (mean +/- SD; p < 0.05), tissue PO2 declined from 28 +/- 4 to 21 +/- 3 mm Hg (p < 0.05), and EEG power fell to approximately 80% of control. During 7-h occlusion, 3-11 DC deflections with a mean duration of 5.2 +/- 4.8 min occurred at irregular intervals, and EEG power gradually declined to 66 +/- 16% of control (p < 0.05). During the passage of DC deflections, LDF did not change, but PO2 further declined to 19 +/- 4 mm Hg (p < 0.05). KCl-induced depolarizations of intact rats were significantly shorter (1.4 +/- 0.5 min; p < 0.05) and were accompanied by a 43% increase in LDF (p < 0.05) and a slight but significant increase in tissue PO2 from 22 +/- 4 to 25 +/- 4 mm Hg (p < 0.05). The comparison of periinfarct and KCl-induced depolarizations demonstrates that oxygen requirements are not coupled to an appropriate flow response in the periinfarct zone with severely reduced blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Diffusion nuclear magnetic resonance imaging in experimental stroke. Correlation with cerebral metabolites.

BACKGROUND AND PURPOSE: Diffusion-weighted nuclear magnetic resonance imaging has been shown to detect early ischemia-related alterations in experimental stroke. This raises the question of whether the observed increase in signal intensity is correlated with changes in cerebral metabolism. After middle cerebral artery occlusion, nuclear magnetic resonance diffusion images were recorded and compared with the regional concentration of cerebral metabolites and with histology of identical planes. METHODS: Seven anesthetized Fischer rats were subjected to permanent occlusion of the middle cerebral artery. T1, T2, and diffusion images (b factors ranging from 0 to 1500 s/mm2) were measured in three to five planes after 7 hours. Thereafter, brains were frozen in situ for histology and quantitative bioluminescence imaging of ATP, glucose, lactate, and for fluorescence imaging of tissue pH. RESULTS: Seven hours after middle cerebral artery occlusion, the apparent diffusion coefficient was reduced from 615 +/- 97 x 10(-6).mm2.s-1 (contralateral brain) to 359 +/- 42 x 10(-6).mm2.s-1 (ischemic brain; mean +/- SD, P < .01). A precise topical coincidence was demonstrated between changes in nuclear magnetic resonance diffusion images, pattern of histological damage, ATP-depleted areas, and local tissue acidosis, the lesion area amounting to between 24.1% and 27.6% of the hemisphere at the level of the caudate-putamen. The area of elevated brain lactate clearly exceeded the acidic core of the infarct and included the slightly alkaline border zone. CONCLUSIONS: The data demonstrate that after 7-hour middle cerebral artery occlusion, the reduction of the apparent diffusion coefficient in nuclear magnetic resonance diffusion images reflects precisely the region of histological injury, breakdown of energy metabolism, and tissue acidosis.

Adenosine Triphosphate↗