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[Magnetic resonance imaging in chronic toluene abuse, and volitional hyperkinesia].

We described the central nervous system impairments and findings of magnetic resonance imaging (MRI) of the brain in three chronic toluene abusers. Patient 1 and 2 had a history of chronic toluene inhalation for 1 or 2 years and patient 3 has a history of it for 16 years. The patients were evaluated after an abstinence period of at least 4 weeks, to avoid neurologic effects of acute intoxication. Neurologic signs included cerebellar, cognitive and pyramidal dysfunctions in all 3 patients and hyperkinésie volitionnelle (HV; volitional hyperkinesia) in patient 3 who had a long history of toluene inhalation. This HV was found to be tremulous by surface electromyography. Appearance of HV in chronic toluene abuse seems to be related to a period or quantity of inhalation of toluene. T2-weighted MRI in the 3 patients revealed the following abnormalities: (1) increased signal intensity of middle cerebellar peduncle and cerebellar white matter, deep cerebral white matter, and posterior limb of internal capsule; and (2) decreased signal intensity of thalamus and basal ganglia. Proton-weighted MRI in patient 3 with HV showed decreased signal intensity of lateral portion of the thalamus and tegmentum of the brainstem. These MRI findings correlate remarkably well with the neurologic signs seen in the 3 patients. Cerebellar, cognitive, and pyramidal dysfunctions appear to be related to involvement of middle cerebellar peduncle (cerebellar white matter), deep cerebral white matter, and internal capsule, respectively, and HV seems to correlate with involvement of the thalamus or tegmentum of the brainstem, especially the latter.

Adult↗

[Protective effects of allopurinol on white matter damage in premature rats].

OBJECTIVE: To investigate the protective effects of allopurinol (ALLO) on white matter damage in premature rats. METHODS: An animal model for white matter damage was established by bilateral carotid artery occulation (BCAO). Eighty-four newborn SD rats (1 day old) were used in this study and were divided randomly into three groups [sham surgery (Sham); BCAO group (BCAO); allopurinol-treated group (ALLO)]. Pathological changes were studied 7 days and 14 days after BCAO, respectively. Myelin basic protein (MBP) was detected by immunohistochemistry 7 days and 14 days after BCAO, respectively. MBP-mRNA expression was determined 7 days and 14 days after BCAO respectively by reverse transcription-polymerase chain reaction (RT-PCR) with fluorescent quantitative method. RESULTS: In BCAO group, mild or severe rarefaction was found in 10 cases in the corpus callosum area, especially at the cingulum. Pathological changes of white matter were found in 4 cases in internal capsule. Subcortex white matter rarefaction was found in 8 cases. The extent of white matter rarefaction in ALLO group was reduced significantly. Enlargement of bilateral ventricles was found in 6 of 8 cases in BCAO group. The average ventricle size in ALLO group (2.44 +/- 0.71)% was reduced significantly as compared with that in BCAO group (3.27 +/- 0.73)% (P < 0.05). Strong MBP positive staining was found in sub-cortex, corpus callosum, hippocampus gyrus, and internal capsule of P14 sham surgery group. In BCAO group the MBP staining extent was reduced. The extent of MBP staining of ALLO group was between the other two groups. The optical density (OD) of MBP positive staining in BCAO group (6.60 +/- 0.68) was found higher than that in sham surgery group (9.40 +/- 0.53), the difference was statistically significant (P < 0.05). Compared with BCAO group, OD value in ALLO group (7.10 +/- 0.18) increased significantly (P < 0.05). RT-PCR data showed that MBP-mRNA copies (log10) in P7 and P14 rats of both BCAO and ALLO groups were lower than that in sham surgery group (P < 0.01); However, MBP-mRNA copies in ALLO group were higher than that in BCAO group (P < 0.05). CONCLUSIONS: BCAO could be used in newborn rats (1 day old) to establish a premature white matter damage (WMD) animal model. Allopurinol may have a potential protective effect on premature SD rat with ischemic WMD.

Allopurinol↗

Cytoarchitectonic heterogeneities in the thalamic reticular nucleus of cats and ferrets.

The thalamic reticular nucleus has been classically defined as a group of cells surrounding most of the rostral and lateral surfaces of the dorsal thalamus, lateral to the fibres of the external medullary lamina and medial to those of the internal capsule. With the use of Nissl staining and antibodies to gamma-aminobutyric acid (GABA), somatostatin, and parvalbumin, this study describes the cytoarchitecture of the thalamic reticular nucleus of cats and ferrets. In cats, three subdivisions of the nucleus are distinguished, two of which are distinct in ferrets also. First, the main body of the reticular nucleus lies lateral to the fibres of the external medullary lamina (except ventrally) and medial to those of the internal capsule. In both cats and ferrets, this structure is heterogeneous, consisting of distinct layers, the details of which vary along the dorsoventral axis. A prominent rostroventral portion of comparatively small rounded cells is also apparent within the main body. Most reticular cells in all areas of the main body are labelled with all of the above mentioned antibodies. Second, the inner small-celled region is a group of small cells located between the external medullary lamina (ventrally) and the medial margin of the ventral regions of the main body of the reticular nucleus: the inner small-celled region is clearly differentiated in cats only. Previous studies have referred to this area as being part of the main body of the reticular nucleus, but we suggest that it may form a separate subnucleus. For example, the inner small-celled region stands in striking contrast to the main body of the reticular nucleus in that none of its cells are GABA immunoreactive and only a small caudal subpopulation are parvalbumin immunoreactive. A very similar pattern of immunostaining is apparent for the cells in the zona incerta, although the latter contains a small rostral subpopulation of GABA immunoreactive cells. Furthermore, although morphologically distinct from the zona incerta, the inner small-celled region fuses with it ventrocaudally. We suggest that the inner small-celled region may constitute a previously undescribed dorsal extension of the zona incerta, rather than a subdivision of the reticular nucleus. Third, the perireticular nucleus, hitherto unidentified, is a discrete group of small cells lateral to the main body of the reticular nucleus and medial to the corpus striatum (globus pallidus and caudate-putamen). It is apparent throughout most of the dorsoventral extent of the main body of the reticular nucleus of cats and ferrets.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Cerebral germinoma with hemiatrophy of the brain: report of three cases.

BACKGROUND: The authors report three cases of cerebral germinoma that occurred in young adults with unusual presentation. METHOD: All three patients presented with hemiparesis and were treated at Seoul National University. A histological diagnosis of germinoma was made by a stereotactic biopsy in all three cases. FINDINGS: Magnetic resonance (MR) images showed that their tumors were located in the internal capsule and thalamus, and were associated with ipsilateral cerebral hemisphere and brain stem atrophy. The hemiparesis slowly progressed and this was accompanied by a haemorrhagic cyst in each patient. INTERPRETATION: Clinical diagnosis was not easy because of the unusual clinical presentations and atypical MR imaging findings. It is suggested that cerebral germinoma should be included in the differential diagnosis of a haemorrhagic mass which is associated with cerebral atrophy in the thalamus, basal ganglia, or internal capsule, especially in adolescents or young adults.

Adolescent↗

Reassessing the Association of Sedentary Behavior and Physical Activity with Ischemic Stroke: A Mendelian Randomization Study.

PURPOSE: Findings from previous Mendelian randomization (MR) studies disagreed with the current scientific consensus regarding the role of physical activity (PA) and sedentary behavior in ischemic stroke (IS). We reassessed these associations with a focus on etiological subtypes of IS and the potential mediating roles of cardiometabolic traits and brain imaging-derived phenotypes (IDPs). METHODS: We performed MR analyses using summary statistics from genome-wide association studies of sedentary behavior and PA ( n = 88,411 ~ 608,595), cardiometabolic traits ( n = 393,193 ~ 694,649), brain IDPs ( n = 33,224), and the latest IS data (62,100 cases and 1,234,808 controls). Inverse-variance weighted regression was used as the primary method, complemented by several sensitivity analyses. A two-step MR approach was employed to assess the mediating effects of cardiometabolic traits and brain IDPs. RESULTS: Genetic liability to leisure-time moderate-to-vigorous PA (MVPA) and higher overall PA (OPA) were associated with reduced risks of IS and small vessel stroke (Benjamini-Hochberg adjusted P < 0.05). Suggestive associations were observed between longer leisure-screen time and higher IS risk and between higher OPA and lower cardioembolic stroke risk ( P < 0.05). The isotropic volume fraction in the anterior limb of the left internal capsule, as well as some cardiometabolic metrics, partially mediated these associations. There was no evidence for causal effects of overall MVPA, overall light-intensity PA, or overall sedentary duration on IS. CONCLUSIONS: Longer leisure screen time, less OPA, and not engaging in MVPA during leisure time were associated with higher risk of IS. The associations between PA and IS depended on different subtypes and were mediated by changes in anterior limb of the left internal capsule and cardiometabolic biomarkers.

Humans↗

Mechanism of reduction of cortical blood flow in striatocapsular infarction: studies using [123I]iomazenil SPECT.

Single photon emission computed tomography (SPECT) using [123I]iomazenil (radioligand of central-type benzodiazepine receptors) was employed to examine two patients with striatocapsular infarction. Patient 1 was a 61-year-old female with motor aphasia and hemiplegia on the right side. Magnetic resonance imaging (MRI) showed a lesion in the anterior limb of internal capsule and putamen on the left side. SPECT using 99mTc-HMPAO revealed a reduction of cerebral blood flow (CBF) in the frontoparietal region on the left side, but the delayed images in SPECT using [123I]iomazenil showed only a mild decrease of accumulation in the frontal lobe. Patient 2 was a 55-year-old male with hemiplegia on the left side. MRI showed a lesion localized in the basal ganglia and posterior limb of the internal capsule on the right side. SPECT using 99mTc-HMPAO revealed a reduction of CBF in the frontoparietal region on the right side and in the cerebellar hemisphere on the left side, but the delayed images in SPECT using [123I]iomazenil showed little decrease of accumulation in parietal lobe. The discrepancy between CBF and receptor images suggested that cortical hypoperfusion on striatocapsular infarction might reflect hypometabolism due to disconnection of the neuronal network between subcortical structure and cortex.

Aphasia↗

Behavioral responses induced by electrical stimulation of the caudate nucleus in freely moving cats.

The caudate nucleus and adjacent structures of 26 freely moving cats were stimulated through multiwire electrodes chronically implanted. Two main effects here observed with trains of pulses of high frequency (100 Hz) and short duration (1 s): (1) contralateral head turning and (2) arrest reaction, which was associated with crouching and escape behavior. The responses follow a certain topographic distribution. Head turning was elicited with the lowest mean threshold in sites located in the internal two-thirds and caudal region of the caudate nucleus, while the arrest reaction was elicited from the ventromedial region of the caudate and adjacent nucleus accumbens. Stimulation of the corpus callosum and internal capsule produces postural instability, ventral flexion of the head and flexion of the contralateral limb. The extra-caudate responses were accompanied by contralateral head turning when the stimulated points were near of the caudate border. Experimental evidence suggested that striatal responses were not due to current spread to adjacent structures or to activation of corticofugal fibers. The head rotation was suppressed following interruption of the ipsilateral striatal outflow by electrolytic lesion of the globus pallidus and adjacent internal capsule. The chemical lesion of the substantia nigra and the ventral pallidum produced a significant increase in the stimulation threshold for head turning and arrest reaction, respectively. These results suggest a topographic arrangement of the responses evoked by electrical stimulation of the caudate nucleus in the cat, which are mediated by the substantia nigra pars reticulata and the ventral pallidum.

Animals↗

Membrane specializations in the developmentally transient perireticular nucleus of the rat.

The perireticular nucleus lies among the fibres of the internal capsule and in the rat is relatively large at birth. Like the subplate of the neocortex, it is dramatically reduced in the adult (Mitrofanis, 1992). On embryonic day 17 (E17), cells of the perireticular nucleus project to the cortex (Adams and Baker, 1995); at birth there is also a projection to the thalamus (Mitrofanis and Baker, 1993). When corticofugal axons reach the perireticular nucleus, they separate into the descending tracts and the corticothalamic pathway. The axons then enter the internal capsule on their way to the thalamus, defasciculate and contribute to a complex zone of interweaving fibres seen in this region (Adams and Guillery, 1994). We have found that the cells of the perireticular nucleus are immunopositive for an antibody (3A10) to a phosphorylated neurofilament protein (Yamada et al., 1991), and we have shown that these 3A10-positive perireticular cells extend their dendrites across the path of cortical fibres at the earliest age studied (E17). We have confirmed this dendritic orientation by Golgi staining at a later stage (P3). Electron micrographs show that axo-somatic and axo-dendritic synapses first appear in the perireticular nucleus at about the day of birth. Prenatally, between E14 and E19, the major specialized membrane interrelationships seen are omega formations between adjacent profiles that often contain vesicles. Omega formations are rarely seen at later stages. Puncta adhaerentia typified by opposing membrane densities with no associated vesicles were seen at all ages studied. We suggest that early membrane contacts (omega formations) may represent transient organisational or guidance influences since they occur during a period when axonal pathways are being defined.

Animals↗

Putaminal haemorrhage leading to pure motor hemiplegia.

Pure motor hemiplegia (PMH) is commonly attributed to lacunar infarction of internal capsule or basis pontis. We report 7 patients of pure motor hemiplegia as a result of small or moderate size putaminal haemorrhage. All the patients had normal median somatosensory evoked potentials. Central Motor Conduction Time (CMCT) to upper limb was not recordable in all 3 patients with complete hemiplegia. Three of seven patients had complete and four had partial recovery. Anterioposterior extension of small or moderate size putaminal haemorrhage seems to spare the medially located sensory fibres in the internal capsule. On the basis of our results, lateral putaminal haemorrhage should be considered in the differential diagnosis of PMH.

Adult↗

Infarcts in the anterior choroidal artery territory. Anatomical distribution, clinical syndromes, presumed pathogenesis and early outcome.

From a prospective registry of all consecutive patients with a supratentorial ischaemic stroke, those with a compatible CT lesion were selected to study topographical relationship, clinical syndrome, vascular risk factors, signs of large-vessel disease or cardiogenic embolism, and mortality in cases with an infarct in the anterior choroidal artery (AChA) territory in comparison with other infarct subtypes. First we identified the area supplied by the AChA: in accordance with the consensus in the literature the posterior two-thirds of the posterior leg of the internal capsule was considered as certain AChA territory. After reviewing CT scans, all presumed small deep AChA territory infarcts were displayed in a schematic composite picture of super-imposed areas of infarction in different shades of grey. Infarcts that were located largely outside the generally included territory were presumed to belong to a different vascular territory. Thus, 77 small deep infarcts were considered to be located within, and 83 outside the AChA territory. Twenty-nine AChA infarcts extended from the internal capsule upwards into the posterior paraventricular corona radiata region. Furthermore, the composite representation of 26 infarcts restricted to the posterior part of the paraventricular corona radiata region showed almost complete overlap with the area occupied by AChA infarcts that extended upwards. We therefore concluded that the posterior paraventricular area is most likely supplied by the AChA. The frequency of a clinical lacunar or a cortical syndrome did not differ between small deep AChA and remaining small deep infarcts. Comparison of vascular risk factors by way of multivariate regression analysis only showed that a significant carotid stenosis was more frequent (adjusted odds ratio 8.87; 95% confidence interval 1.44-54.50), and a cardioembolic source was less frequent (odds ratio 0.24; 95% confidence interval 0.07-0.92) in AChA infarcts than in the other small deep infarcts. Carotid stenosis and cardiac embolism were less frequent in AChA infarcts than in superficial infarcts (odds ratio 0.33, 0.23, respectively; 95% confidence interval 0.15-0.74, 0.09-0.52, respectively). One month and one year mortality were lower in small deep infarcts compared with superficial infarcts, but most favourable in the AChA group. However, this was probably related to younger age in the AChA patients. Larger AChA infarcts were infrequent in our series; six of such cases did not differ in any respect from superficial infarcts. We conclude that the posterior paraventricular corona radiata region is most likely supplied by the AChA, and that AChA infarcts do not constitute a separate brain infarct entity.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

Infarcts in the territory of lenticulostriate branches from the middle cerebral artery. Etiological factors and clinical features in 65 cases.

We studied 65 consecutive patients with a first stroke who had an appropriate CT-proven small infarct in the territory of the lateral (61 patients), medial (3 patients) or both lateral and medial lenticulostriate arteries (1 patient) from the middle cerebral artery. While more than 75% of these patients were either hypertensive or diabetic (having at least one cause for small-artery disease), embolic sources were encountered in 35%, either from large vessels (28%), and/or from the heart (15%). Other causes (angiitis, migraine) were found in only 9%. The neurologic deficit was purely motor in more than 50% of the patients (in half of them with neuropsychological dysfunctions), a sensori-motor deficit was present in 30% (in half of them with neuropsychological dysfunctions), and only 20% had ataxic hemiparesis. No one had pure sensory stroke. None of the classical lacunar syndrome or the modality of sensory, motor or ataxic deficits were specific for any topographic subdivision of LS territory, but there was a tendency for clinical features to be linked with the involved basal ganglia and the topography of pathways in the internal capsule as delineated by anatomical studies. Pure motor deficits were associated with infarcts in the medial and posterior part of LS territory, visual field deficits and hemineglect always corresponded to posteriorly situated infarcts. Neuropsychological deficits were common in infarcts in the anterior and posterior subdivisions of LS territory, with a major effect of the size of infarct. Sensory deficits were not correlated with any location in LS territory, probably because thalamo-efferent fibres have a more diffuse course through the internal capsule.

Aged↗

Drainage of interstitial fluid from different regions of rat brain.

Studies were carried out in anesthetized rats comparing dynamics and pathways of interstitial fluid (ISF) drainage from different regions of brain. Rates of drainage from brain and flow into cerebrospinal fluid (CSF) were estimated from the efflux from brain and influx into CSF of radioiodinated albumin (RISA) following microinjection into caudate nucleus, internal capsule, or midbrain: pathways of flow through the subarachnoid space and into lymph were traced from the distribution of horseradish peroxidase and/or Evans blue-labeled albumin after injection into brain. ISF drainage rates (mul X g brain-1 X min-1) estimated for the three injection sites were 0.18, 0.19, and 0.29, respectively. Flow of ISF into bulk CSF sampled from the cisterna magna accounted for 60-75% of efflux from midbrain but only 10-15% of efflux from caudate nucleus or internal capsule. RISA was concentrated in the subarachnoid space, relative to bulk CSF, in sleeves of adventitial tissue surrounding pericerebral arteries, possibly accounting for the low recovery of isotope from bulk CSF. From the subarachnoid space, some fluid drained via olfactory nerve sheaths to retropharyngeal lymph nodes.

Animals↗

Diffusion tensor imaging of partial intractable epilepsy.

Our aim was to assess the value of diffusion tensor imaging (DTI) in patients with partial intractable epilepsy. We used DTI (25 non-collinear directions) in 15 patients with a cortical lesion on conventional MRI. Fractional anisotropy (FA) was measured in the internal capsule, and in the normal-appearing white matter (WM), adjacent to the lesion, and away from the lesion, at a set distance of 2-3 cm. In each patient, increased or decreased FA measurements were those that varied from mirror values using an arbitrary 10% threshold. Over the whole population, ipsi- and contralateral FA measurements were also compared using a Wilcoxon test (p<0.05). Over the whole population, FA was significantly reduced in the WM adjacent to and away from the lesion, whilst being normal in the internal capsule. FA was reduced by more than 10% in the WM adjacent to and distant from the lesion in 13 and 12 patients respectively. For nine of the ten patients for whom the surgical resection encompassed the limits of the lesion on conventional MRI, histological data showed WM alterations (gliosis, axonal loss, abnormal cells). DTI often reveals WM abnormalities that are undetected on conventional MRI in patients with partial intractable epilepsy.

Adolescent↗

Subcellular localization of type 1 cannabinoid receptors in the rat basal ganglia.

Endocannabinoids, acting via type 1 cannabinoid receptors (CB1), are known to be involved in short-term synaptic plasticity via retrograde signaling. Strong depolarization of the postsynaptic neurons is followed by the endocannabinoid-mediated activation of presynaptic CB1 receptors, which suppresses GABA and/or glutamate release. This phenomenon is termed depolarization-induced suppression of inhibition (DSI) or excitation (DSE), respectively. Although both phenomena have been reported to be present in the basal ganglia, the anatomical substrate for these actions has not been clearly identified. Here we investigate the high-resolution subcellular localization of CB1 receptors in the nucleus accumbens, striatum, globus pallidus and substantia nigra, as well as in the internal capsule, where the striato-nigral and pallido-nigral pathways are located. In all examined nuclei of the basal ganglia, we found that CB1 receptors were located on the membrane of axon terminals and preterminal axons. Electron microscopic examination revealed that the majority of these axon terminals were GABAergic, giving rise to mostly symmetrical synapses. Interestingly, preterminal axons showed far more intense staining for CB1, especially in the globus pallidus and substantia nigra, whereas their terminals were only faintly stained. Non-varicose, thin unmyelinated fibers in the internal capsule also showed strong CB1-labeling, and were embedded in bundles of myelinated CB1-negative axons. The majority of CB1 receptors labeled by immunogold particles were located in the axonal plasma membrane (92.3%), apparently capable of signaling cannabinoid actions. CB1 receptors in this location cannot directly modulate transmitter release, because the release sites are several hundred micrometers away. Interestingly, both the CB1 agonist, WIN55,212-2, as well as its antagonist, AM251, were able to block action potential generation, but via a CB1 independent mechanism, since the effects remained intact in CB1 knockout animals. Thus, our electrophysiological data suggest that these receptors are unable to influence action potential propagation, thus they may not be functional at these sites, but are likely being transported to the terminal fields. The present data are consistent with a role of endocannabinoids in the control of GABA, but not glutamate, release in the basal ganglia via presynaptic CB1 receptors, but also call the attention to possible non-CB1-mediated effects of widely used cannabinoid ligands on action potential generation.

Action Potentials↗

Diffusion tensor imaging of the corticospinal tract following cerebral hemispherectomy.

Following cerebral hemispherectomy, the corticospinal tract is believed to undergo reorganizational changes, which can induce enhanced function of the contralateral motor pathway and mediate partial recovery of motor function. The aim of this study was to use diffusion tensor imaging to investigate the effects of hemispherectomy on the corticospinal tract, with particular attention to the corticospinal tract contralateral to the resection. Diffusion tensor imaging would presumably detect microstructural abnormalities through quantitative measurements of the fiber tract integrity and orientation. Four patients with anatomic hemispherectomy and three patients with subtotal hemispherectomy were examined and compared with age-matched normal controls. Apparent diffusion coefficient and fractional anisotropy values were measured in regions along the corticospinal tract: internal capsule, cerebral peduncle, rostral pons, midpons, and caudal pons. None of the patients with anatomic hemispherectomy or subtotal hemispherectomy showed significant changes in either apparent diffusion coefficient or fractional anisotropy values in the corticospinal tract contralateral to the resected hemisphere, whereas increased apparent diffusion coefficient and decreased fractional anisotropy were observed in the ipsilateral rostral pons, midpons, and caudal pons of all patients with anatomic hemispherectomy, as well as in the ipsilateral cerebral peduncle of one patient with subtotal hemispherectomy. Increased apparent diffusion coefficient values were also noted in the ipsilateral internal capsule of the same patient. This study revealed no evidence of significant reinforcement of the contralateral corticospinal tract in patients with hemispherectomy, at least from diffusion tensor imaging measurements, but suggests that wallerian degeneration most likely occurs in the ipsilateral motor pathway.

Adolescent↗

[A case with pyramidal tract lesion suggesting Wallerian degeneration--analysis with diffusion coefficient].

We reported a 55-year-old man, whose T2-weighted MR images disclosed abnormal high signal band along the left pyramidal tract 6 months after cerebral infarction of the left centrum semiovale. Brain CT revealed low intensity areas in the centrum semiovale, the posterior limb of the internal capsule on left side. On T2-weighted MR images, there were an irregular high signal area on the left centrum semiovale, a high signal band from the left centrum semiovale to the medullary pyramid, and a high signal band from the left centrum semiovale to the cerebral cortex. These lesions were observed as high signal areas on proton weighted images and low signal areas on T1-weighted MR images. Diffusion coefficient perpendicular to the pyramidal tract in the patient, which was calculated from diffusion weighted images at the posterior limb of the internal capsule, was higher than that in normal individuals. Diffusion anisotropy at the lesion, which is the rate between the diffusion coefficient parallel and perpendicular to nerve fiber, was higher than that of normal individuals. These data suggested that the lesion had demyelinating process, which was consistent with the pathology at stage 2 of the Wallerian degeneration.

Cerebral Infarction↗

Fetal hypothalamic transplants into brain irradiated rats: graft morphometry and host behavioral responses.

This study was designed to test the hypothesis that neural implants can ameliorate or prevent some of the long-term changes associated with CNS irradiation. Using a rat model, the initial study focused on establishing motor, regulatory, and morphological changes associated with brain radiation treatments. Secondly, fetal hypothalamic tissue grafts were placed into the third ventricle of rats which had been previously irradiated. Adult male Long Evans rats received one of three radiation doses (15, 22.5, & 30 Gy) or no radiation. Three days after irradiation, 7 animals in each dose group received an embryonic day 17 hypothalamic graft into the third ventricle while the remaining 8-9 animals in each group received injections of vehicle solution (sham). Few changes were observed in the 15 and 22.5 Gy animals, however rats in the 30 Gy treatment group showed stereotypic and ambulatory behavioral hyperactivity 32 weeks after irradiation. Regulatory changes in the high dose group included decreased growth rate and decreased urine osmolalities, but these measures were extremely variable among animals. Morphological results demonstrated that 30 Gy irradiated animals showed extensive necrosis primarily in the fimbria, which extended into the internal capsule, optic nerve, hippocampus, and thalamus. Hemorrhages were found in the hippocampus, thalamus, and fimbria. Defects in the blood brain barrier also were evident by entry of intravascularly injected horseradish peroxidase into the parenchyma of the brain. Animals in the 30 Gy grafted group showed fewer behavioral changes and less brain damage than their sham grafted counterparts. Specifically, activity measures were comparable to normal levels, and a dilute urine was not found in the 30 Gy implanted rats. Morphological changes support these behavioral results since only two 30 Gy implanted rats showed necrosis in the fimbria, internal capsule, and other areas of the brain. These results suggest that grafts of fetal neural tissue exert a beneficial influence on the host brain, although the mechanism by which the implant exerts its effect is still unknown. Evidence supporting the role of trophic factors is reviewed. These preliminary results suggest a potential for tissue grafts in the treatment of CNS irradiated patients.

Animals↗

I-123 hydroxyiodobenzyl propanediamine (HIPDM) cerebral blood flow imaging demonstrating transtentorial diaschisis.

To assess the clinical significance of transtentorial diaschisis (TTD) as demonstrated by I-123 HIPDM brain imaging, SPECT and/or planar images of 35 patients with stroke, 26 patients with Alzheimer's disease (AD), 2 patients with Creutzfeldt-Jakob disease (CJD), and 1 patient with a schizoaffective disorder were analyzed. TTD was observed in 21 of the 35 patients with strokes. In 13 stroke patients, TTD was associated with large infarcts in the middle cerebral artery (MCA) territory; in the remaining 8 stroke patients, TTD was associated with internal capsule and/or basal ganglia infarcts. TTD was not associated with small occipital or parietal infarcts. Despite cortical perfusion decrements, TTD was not seen in the AD patients, the CJD patients, or the patient with schizoaffective disorder. It is concluded that 1) TTD frequently occurs following cerebral infarct of the MCA territory (60% of the patients in this sample); 2) absence of TTD in the presence of a large cerebral perfusion abnormality may represent neuronal dysfunction of the cerebral cortex; and 3) the presence of TTD without a significant cortical perfusion abnormality may indicate basal ganglia and/or internal capsule infarct.

Alzheimer Disease↗