Search PubMed⌕ Search

Biomedical subjects

A Nehlig

Publications and source records attributed to A Nehlig.

At least 19 recordsLinked to original sources
PubMed1997

Transport of alpha-ketoisocaproate in neuroblastoma NB-2a cells.

Transport of alpha-ketoisocaproate (KIC), a ketoacid originating from leucine and proposed to be involved in the buffering of glutamate in neurones, was studied in neuroblastoma NB-2a cells. The accumulated KIC was mostly transaminated to leucine, while free keto-acid was detectable either only after prolonged times or after inhibiting transaminase with aminooxyacetate. Accumulation of KIC was found to be inhibited by other branched-chain ketoacids, while lactate and beta-hydroxybutyrate were ineffective. The transport of KIC, resembling a facilitated diffusion, was decreased by phloretin, alpha-cyano-4-hydroxycinnamate, 4,4'-diisothiocyano-2,2'-stilbenedisulphonate, and p-chlorimercuribenzoate. The process of accumulation did not resemble a symport with protons; therefore an involvement of the known proton-coupled monocarboxylate transporters (MCT) was excluded. Distribution of KIC suggests a mechanism involving a cotransport with 2 [Na+].

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1997

Forebrain metabolic activation induced by the repetition of audiogenic seizures in Wistar rats.

In Wistar rats susceptible to audiogenic seizures (Wistar AS) inbred in our laboratory, the exposure to an intense sound induces an epileptic seizure characterized by a running episode followed by a tonic phase showing the major involvement of brainstem structures. After 10-20 sound-induced seizures, development of facial and forelimb clonus and/or tonic-clonic seizures characterize the generalization from brainstem to the forebrain as a result of seizure repetition. In order to specify the anatomical substrates of repeated audiogenic seizures in Wistar AS, we used the 2-deoxyglucose (2DG) technique over a 5 min period to map the midbrain and forebrain structures activated by audiogenic seizures before and after seizure repetition. In naive Wistar AS, six of the 22 structures showed a significant 20-56% increase in relative optical densities compared to non-epileptic controls; these were central and medial amygdala nuclei, perirhinal cortex, medial septum, subthalamic and caudate nuclei. In kindled Wistar AS, 12 additional structures showed a significant 16-121% increase in 2DG labeling. These structures were the substantia nigra, all layers of the hippocampus, the basolateral amygdala, three thalamic nuclei, the frontal motor and prefrontal cortices. In conclusion, the metabolic activation of midbrain and forebrain areas in kindled versus naive Wistar AS rats reflects the changes in the nature of the seizures and the involvement of these structures in the spread of seizure activity from the brainstem to the forebrain during seizure repetition.

Acoustic Stimulation↗
PubMed1997

The amygdala is critical for seizure propagation from brainstem to forebrain.

Audiogenic seizures, a model of brainstem epilepsy, are characterized by a tonic phase (sustained muscular contraction fixing the limbs in a flexed or extended position) associated with a short cortical electroencephalogram flattening. When sound-susceptible rats are exposed to repeated acoustic stimulations, kindled audiogenic seizures, characterized by a clonic phase (facial and forelimb repetitive jerks) associated with cortical spike-waves, progressively appear, suggesting that repetition of brainstem seizures causes a propagation of the epileptic discharge toward the forebrain. In order to determine the structures through which this propagation occurs, four kinds of experiments were performed in non-epileptic rats and in sound-susceptible rats exposed to single or repeated sound stimulations. The following results were obtained: (I) Electrical amygdalar kindling was similar in non-epileptic and naive-susceptible rats, but was facilitated in sound-susceptible rats submitted to 40 acoustic stimulations and presenting kindled audiogenic seizures. (2) Audiogenic seizures induced an increase in [(14)C]2-deoxyglucose concentration in the amygdala after a single seizure, and in the amygdala, hippocampus and perirhinal and piriform cortices after a kindled audiogenic seizure. (3) A single audiogenic seizure induced the expression of c-Fos protein mainly in the auditory nuclei. A few cells were stained in the amygdala. After 5-10 audiogenic seizures, a clear staining appeared in the amygdala, and perirhinal and piriform cortices. The hippocampus expressed c-Fos later, after 40 audiogenic seizures. (4) Injection of lidocaine into the amygdala did not modify single audiogenic seizures, but suppressed myoclonias and cortical spike-waves of kindled audiogenic seizures. Similar deactivation of the hippocampus failed to modify kindled audiogenic seizures. Taken together, these data indicate a critical role for the amygdala in the spread of audiogenic seizures from brainstem to forebrain.

Acoustic Stimulation↗
PubMed1997

Cerebral energy metabolism, glucose transport and blood flow: changes with maturation and adaptation to hypoglycaemia.

Brain maturation is characterized by a peak of cerebral energy metabolism and blood flow occurring between 3 and 8 years of age in humans and around 14-17 days of postnatal life in rats. This high activity coincides with the period of active brain growth. The human brain is dependent on glucose alone during that period, whereas rat brain uses both glucose and ketone bodies to cover its energetic and biosynthetic needs. The maturation of the density of glucose transporter sites-GLUT1 located at the blood-brain barrier and GLUT3 at the neuronal membrane-parallels the development of cerebral glucose utilization. During moderate acute hypoglycaemia, there are no changes in cerebral functional activity; cerebral glucose utilization decreases and blood flow increases only when hypoglycaemia is severe (lower than 2 mumol/ml). During chronic hypoglycaemia, the brain adapts to the low circulating levels of glucose: the number of glucose transporter sites is increased, and cerebral glucose utilization and function are maintained at normal levels while cerebral blood flow is more moderately increased than during acute hypoglycaemia. Neuronal damage consecutive to severe and prolonged hypoglycaemia occurs mainly in the cerebral cortex, hippocampus and caudate-putamen as a result of active release of excitatory amino acids.

Adaptation, Physiological↗
PubMed1997

Cerebral metabolic consequences of neonatal pathologies in the immature rat.

The cerebral metabolic consequences of hypoxia, seizures and hyperbilirubinemia were explored in immature rates between the postnatal age of 10 (P10) and 21 days (P21) by the quantitative autoradiographic [14C]2-deoxyglucose technique. The effects of a previous bilirubin exposure on cerebral regional permeability to bilirubin were measured by autoradiography. Hypoxia was induced by breathing a 7% N2/93% O2 gas mixture and seizures were initiated by injections of pentylenetetrazol. Hyperbilirubinemia was induced by the perfusion of a bilirubin/albumin solution. Hypoxia and seizures induced a general increase in cerebral metabolic rates to glucose (LCMRglc) in P10 rats, except in hippocampus during seizures. At P14, LCMRglc remained increased during seizures, except in the hippocampus. During hypoxia LCMRglc were unchanged in the genu of the corpus callosum and the anterior commissure and decreased in the cerebellar white matter. At P21, LCMRglc decreased in all white matter regions during hypoxia and in the hippocampus during seizures, while they were unchanged in the amygdala and increased in the nucleus of the solitary tract. During hyperbilirubinemia, LMCRglc decreased at all ages with very marked changes in the nucleus of the auditory nerve at P10 and in the inferior colliculus at P21 (72-86%). Twofold decreases were also recorded in the hippocampus. The basic regional cerebral permeability to the anion was higher at P10 than P21 and the marked increases in regional permeability to bilirubin after a previous exposure to the anion were located in the nucleus of the auditory nerve and the hippocampus.

Age Factors↗
PubMed1996

Interictal cerebral metabolic levels in Wistar rats sensitive to audiogenic seizures.

In the present study, we compared interictal local cerebral metabolic rates for glucose (LCMRglcs) in a strain of audiogenic rats (Wistar AS) selected in our laboratory to interictal LCMRglcs in a strain of control non-epileptic (NE) rats. Two groups of Wistar AS were studied, one group exposed to a single audiogenic seizure and one group of kindled rats exposed to 40 daily repetitive seizures. Control NE animals were exposed to a single sound exposure which did not induce any behavioral disturbance. Interictal LCMRglcs were measured by the quantitative autoradiographic [14C]2-deoxyglucose technique 5 days after the last sound exposure. LCMRglcs were similar in the three groups of rats in 80% of the structures. Compared to the control NE strain, interictal metabolic levels were mainly decreased in auditory structures of Wistar AS, either naive or kindled, thus confirming auditory impairment in audiogenic animals. LCMRglcs were increased over control levels in both groups of Wistar AS in cerebellar regions. This increase of cerebellar functional activity in Wistar AS compared to control NE rats might reflect an increased cerebellar input which, together with auditory impairment, may facilitate the induction of seizure activity in Wistar AS. Finally, there was no difference between the interictal cerebral metabolic level of naive and kindled Wistar AS, except in the cerebellar dentate nucleus where LCMRglc was significantly higher in kindled than in naive animals.

Acoustic Stimulation↗
PubMed1996

The model of pentylenetetrazol-induced status epilepticus in the immature rat: short- and long-term effects.

In order to assess acute, short and long-term effects of seizures in the immature rat brain, we studied the metabolic, circulatory and histopathological changes induced by pentylenetetrazol (PTZ) given at postnatal day 10 (P10) or 21 (P21). Seizures were induced by repetitive subconvulsive injections of PTZ given as a first dose of 40 mg/kg followed 10 min later by 20 mg/kg. Thereafter, rats received every 10 min additional injections of PTZ 10 mg/kg until the onset of status epilepticus. Local cerebral metabolic rates for glucose (LCMRglc) were measured both during the seizures in P10 and P21 rats and in the young adult animal at P60 by means of the quantitative 2-deoxyglucose technique. Rates of local cerebral blood flow (LCBF) were determined during the seizures by the iodoantipyrine technique. Short-term histological changes were assessed by acid fuchsin and hematoxylin-eosin staining and by HSP72 immunohistochemistry. At P10, LCMRglcs uniformly increased (38-400%) over control values during seizures. At P21, metabolic increases (39-181%) occurred only in 20% of the structures while LCMRglcs decreased in most cortical, hippocampal and sensory areas as well as in mammillary body, discrete thalamic nuclei and white matter areas. At P10, LCBF rose (32-184%) in all brain structures whereas, at P21, LCBF decreased in cortical, hippocampal and sensory regions and increased in most other areas. At P60, in animals having seized at either age, significant long-term decreases in LCMRglcs were recorded in hippocampus, auditory and piriform cortex, medial geniculate body and mammillary body. In P60 animals exposed to PTZ at P10, LCMRglcs were also decreased in 3 other sensory areas. In P60 animals exposed to seizures at P21, LCMRglcs were additionally decreased in sensory regions, cortices, thalamic and hypothalamic regions. Neuronal cells were transiently stained with acid fuchsin, with a peak occurring at 24 h after the seizures. The stain was visible in all regions of cerebral cortex and hippocampus and in some thalamic and hypothalamic nuclei. This transient staining was not accompanied by cell degeneration as assessed by hematoxylin-eosin histology. No HSP72 expression could be detected 24 h after the seizures, neither at P10 nor at P21. The present study shows that the immature rat neurons undergo altered metabolic rates and local circulatory decreases in the acute phase, a change in the affinity of acid fuchsin as a short-term effect and long-term metabolic decreases. All these changes are located in the same regions, i.e., cerebral cortex, hippocampus, sensory regions as well as scattered thalamic and hypothalamic nuclei. Thus, short- and long-term metabolic changes induced by seizures can be used as an index of cell stress in the immature rat brain. Since all these changes occur in the absence of visible neuronal death, they might be related to changes in the final arborization and synaptic organization of the developing brain.

Animals↗
PubMed1996

Absence seizures induce a decrease in cerebral blood flow: human and animal data.

Our previous studies on cerebral metabolic activity in genetic absence epilepsy rats from Strasbourg (GAERS) were in favor of decreased functional activity during absences and normal or increased interictal activity. To ascertain that hypothesis, in the present study we performed continuous measurements of CBF in both children with typical absence epilepsy and GAERS, using Doppler ultrasonography and laser-Doppler flowmetry, respectively. CBF fluctuations during absences were recorded in four children between 5 and 6 years of age and 16 adult GAERS. In both children and animals, CBF measured in the middle cerebral artery and cortical capillaries, respectively, significantly decreased by a median value of 20-24% under basal levels during spontaneous absences. In GAERS, CBF levels were continuously decreased during haloperidol-induced absence status epilepticus, while they were not affected by ethosuximide. Conversely, convulsive seizures induced in rats either by kainate or picrotoxin led to a 175-664% increase in CBF levels. In conclusion, the present data show that during spontaneous absences, CBF decreases under basal levels in both cortical capillaries (GAERS) and the middle cerebral artery (children). Moreover, these fluctuations occur in vessels with normal vascular reactivity, are not mediated by changes in PO2, PCO2, or arterial blood pressure, and represent rather a response to reduced metabolic demand.

Animals↗
PubMed1996

Respective roles of glucose and ketone bodies as substrates for cerebral energy metabolism in the suckling rat.

The postnatal evolution of local cerebral metabolic rates for glucose (LCM-Rglcs) and of regional rates of cerebral uptake of beta-hydroxybutyrate (beta HB) were studied in the suckling rat between postnatal days (P) 10 and 21. LCM-Rglcs were low and homogeneous at P10. They increased significantly in 4 auditory regions between P10 and P14 at the time of maturation of the auditory function. Between P14 and P17, they increased further in 2 auditory regions, in 1 visual area, the lateral geniculate nucleus, and 3 limbic and 3 motor areas. These increases occurred simultaneously with the maturation of vision and with the development of the rat locomotion and behavioral activities. Between P17 and P21, LCMRglcs increased in all areas studied. Conversely to the function-related increases in LCMRglcs, regional rates of cerebral beta HB uptake showed an overall increase between P10 and P14, stayed very high until P17 and did not correlate with the maturation of the rat behavior. Between P17 and P21, rates of cerebral beta HB uptake decreased significantly in all regions studied. In conclusion, it appears that, even in the rat whose cerebral metabolic activity depends upon both glucose and ketone bodies during suckling, postnatal increases in LCMRglcs represent a signal of the acquisition of new functions and neurological competence.

3-Hydroxybutyric Acid↗
PubMed1996

Autoradiographic mapping of local cerebral permeability to bilirubin in immature rats: effects of hyperbilirubinemia.

Kernicterus is characterized by the accumulation of bilirubin mainly into subcortical brainstem nuclei. Inasmuch as premature infants are more susceptible to kernicterus, we hypothesized that the cerebral permeability to bilirubin could vary by cerebral region and with age. Therefore, in the present study, we measured the blood-to-brain transfer constant (Ki) of [3H]bilirubin in 6-8 rats at postnatal age 10 (P10) or 21 d (P21) in basal conditions and after a bilirubin perfusion to explore age-related and bilirubin-induced changes in the cerebral permeability to the dye. Blood-to-brain transfer of [3H]bilirubin was measured in 39 brain regions by quantitative autoradiography in 15-min experiments. Rats exposed to unlabeled bilirubin received a loading dose of 160 mg/kg over 15 min followed by a 90-min bilirubin perfusion at a speed of 64 mg/kg/h. At P10, cerebral permeability to bilirubin ranged from 0.07 to 0.12 microL/g/min, except in the auditory nerve, dentate nucleus, hypothalamus, and thalamus where it reached 0.41-0.47 microL/g/min. At P21, Ki of bilirubin was significantly lower than at P10 and ranged from 0.03-0.06 microL/g/min in most brain areas. In P10 bilirubin-exposed rats, permeability to bilirubin significantly increased over control levels in all brain regions but three. The largest increases (> 350%) were recorded in the sensory regions, most limbic areas, hypothalamus, and thalamus. At P21, hyperbilirubinemia induced increases in blood-to-brain transfer of bilirubin of 50-200% in 16 brain areas, except in the hippocampus, sensory-motor cortex, and thalamic nuclei where they reached 200-433%. Thus, it appears that the immature rat brain (P10) is very permeable to bilirubin. The increased permeability with preexposure to the dye, especially in brain regions which are affected in infants with kernicterus, could be related either to the large decrease in the value of the albumin:bilirubin ratio between control (15-16) and hyperbilirubinemic conditions (1.7-1.8) and/or to an increased permeability to bilirubin.

Age Factors↗
PubMed1995

Mapping of the consequences of bilirubin exposure in the immature rat: local cerebral metabolic rates for glucose during moderate and severe hyperbilirubinemia.

The regional cerebral metabolic consequences of bilirubin intoxication are not well known. With the quantitative autoradiographic [14C]2-deoxyglucose (2DG), we studied the effect of moderate or severe bilirubin infusion on local cerebral metabolic rates for glucose utilization (LCMRglcs) in 10 (P10) and 21 day-old (P21) rats. After an 80 or 160 mg/kg loading dose of bilirubin administered over 15 min, the speed of bilirubin infusion was reduced to 32 or 64 mg/kg/h for the following 105 min, for moderate or severe intoxication, respectively. This infusion protocol led to plasma bilirubin concentrations of 100-200 nmol/ml (moderate intoxication) or 200-300 nmol/ml (severe intoxication). Cerebral bilirubin concentration was 10 nmol/g at P10 and undetectable at P21 in moderate hyperbilirubinemia while it reached 22-34 nmol/g at both ages during severe hyperbilirubinemia. At P10, bilirubin infusion, moderate or severe, induced significant decreases in LCMRglcs in 17 and 15 brain regions of the 24 studied, respectively. At P21, moderate hyperbilirubinemia induced a decrease in LCMRglcs in only 2 regions, auditory cortex and auditory nerve. Conversely, at that age, severe bilirubin intoxication led to significant decreases in LCMRglcs in all regions studied. These results demonstrate that metabolic changes induced by bilirubin are directly correlated to its entry into the brain which occurs without any alteration in the blood-brain barrier. Indeed, the effects of the dye are quite discrete during moderate hyperbilirubinemia at P21 when no bilirubin is detectable in the brain while they are massive during severe hyperbilirubinemia at P21 and at both levels of intoxication at P10 when bilirubin has entered the brain in measurable amounts.

Animals↗
PubMed1995

Regional cerebral metabolic consequences of bilirubin in rat depend upon post-gestational age at the time of hyperbilirubinemia.

While the accumulation of bilirubin in specific brain regions has been well characterized at autopsy in kernicteric infants, data on the regional effects of early cerebral bilirubin intoxication are still missing. Therefore, the quantitative autoradiographic [14C]2-deoxyglucose technique was applied to the measurement of the effects of a bilirubin infusion on local cerebral metabolic rates for glucose (LCMRglc) in immature rats. A loading dose of 80 mg/kg bilirubin was first administered to the animals over 15 min. Thereafter, the velocity of the infusion was reduced to 32 mg/kg/h and the infusion was continued for 105 min. The animals were studied at two ages, postnatal day 10 (P10) and P21. The [14C]2-deoxyglucose was injected to the animals 45 min before the end of the infusion. Bilirubin infusion led to plasma concentrations ranging from 100 to 200 mumol/l at both ages and to brain amounts of 10-16 nmol/g at P10 while bilirubin was not detectable in brain at P21. Hyperbilirubinemia induced widespread decreases in LCMRglcs at P10 and had rather limited consequences on cerebral glucose utilization at P21. At P10, decreases in LCMRglcs were mostly prominent in regions that have been shown to preferentially accumulate bilirubin in kernicteric infants. In conclusion, there appears to be a good correlation between these metabolic data and regional brain permeability to bilirubin.

Aging↗
PubMed1995

Behavioral and metabolic consequences of neonatal exposure to diazepam in rat pups.

The short-term consequences of a neonatal exposure to diazepam (DZP) on neurobehavioral development and postnatal changes in local cerebral metabolic rates for glucose (LCMRglcs) in selected regions were studied in rats. Rat pups received a daily subcutaneous injection of 10 mg/kg DZP or of the dissolution vehicle from Postnatal Day 2 (P2) to 21 (P21). DZP did not affect the static righting reflex tested at P4 but increased suspension time at P10 and time to complete a 180 degrees pivoting on an inclined plane at P9. In a locomotor coordination test performed at P20, swimming or climbing on a vertical pole was not affected by DZP while the drug impaired the ability of the rat to place its hind-paws on the horizontal platform after climbing. Likewise, DZP induced marked decreases (19-45%) in LCMRglcs in most structures studied at P10, P14, and P21. The results of the present study show that neonatal DZP treatment induces motor deficits that appear to be quite subtle, to concern mainly posture and body balance. They are not apparent in tasks such as swimming or climbing but become obvious in more difficult tasks such as achieving a horizontal quadruped position on a platform after a climbing phase. Decreases in cerebral energy metabolism appear to be mainly located in areas controlling posture and body balance and are partly correlated with the locomotor impairments recorded in the present study.

Animals↗
PubMed1995

Long-term metabolic effects of pentylenetetrazol-induced status epilepticus in the immature rat.

The present study was devoted to the long-term effects of seizures induced by pentylenetetrazol in immature rats on cerebral metabolic rates in young adult animals. Seizures were induced by repetitive intraperitoneal injections of subconvulsive doses of pentylenetetrazol either in 10- (P10) or in 21- (P21) day-old rats. The long-term metabolic effects of the seizures were studied at P60 in 54 cerebral structures by means of the [14C]deoxyglucose method. At P60, metabolic activity was decreased in 10 brain regions of rats exposed to pentylenetetrazol at P10 and in 29 structures in rats exposed to seizures at P21. Among the structures whose metabolic activity was reduced at P60 by seizures occurring either at P10 or at P21 were mainly sensory, cortical and hippocampal regions plus mammillary body, i.e. all the structures metabolically characterized as most vulnerable to pentylenetetrazol-induced status epilepticus in our previous study [Pereira de Vasconcelos A. et al. (1992) Devl Brain Res. 69, 243-259]. In the animals exposed to seizures at P21, metabolic activity was also reduced at P60 in additional sensory and cortical regions, as well as in limbic, thalamic and hypothalamic nuclei, also considered as highly sensitive to short-term pentylenetetrazol-induced seizures [Pereira de Vasconcelos A. et. al. (1992)]. Rates of glucose utilization were also reduced in a few additional areas such as the monoaminergic cell groupings. In conclusion, there are some parallels between the structures metabolically most sensitive during pentylenetetrazol-induced status epilepticus in immature rats and the long-term regional metabolic decreases recorded at P60. Our data also confirm the well-known higher sensitivity to seizures during the third postnatal week in rodents.

Aging↗
PubMed1995

Changes in transport of [14C] alpha-aminoisobutyric acid across the blood-brain barrier during pentylenetetrazol-induced status epilepticus in the immature rat.

In the present study, we measured the effects of pentylenetetrazol (PTZ)-induced status epilepticus on the blood-brain barrier (BBB) permeability in rats at postnatal age 10 (P10) or 21 days (P21). Seizures were induced by the repetitive injection of subconvulsive doses of PTZ until the onset of status epilepticus characterized as the loss of quadruped posture. The BBB permeability changes to the poorly diffusible amino acid [14C] alpha-aminoisobutyric acid (AIB) were measured by autoradiography at 10 min after the onset of status epilepticus. Seizures induced a generalized increase in BBB permeability to AIB that was significant in 22 and 26 regions out of the 34 studied at P10 and P21, respectively. Highest increases over control levels (> 250%) were recorded at both ages in interpeduncular nucleus, raphe nuclei and trigeminal nerve tractus. Quite high increases (> 150%) were recorded in cortical, inferior collicular and thalamic areas at P10 and in inferior colliculus, cerebellar cortex, hypothalamic and thalamic regions at P21. Cerebral blood volume measured with [14C]sucrose over a 2-min period was significantly increased over control levels in hypothalamus and cerebellum at P10 and in all brain regions, except hippocampus and brainstem, at P21. The widespread increase in BBB permeability is at least partly related to the blood pressure increase, 55 and 22% over control values at P10 and P21, respectively. In the P10 rat, generalized BBB leakage appears to be correlated to the widespread increase in cerebral metabolic and blood flow rates that we recorded previously in the same experimental conditions. Conversely, at P21, as previously shown in adults, there is a mismatch between the nature of the structures with increased BBB permeability and the regional distribution of cerebral blood flow and metabolism changes induced by PTZ seizures.

Aminoisobutyric Acids↗
PubMed1995

Mapping of cerebral blood flow changes during audiogenic seizures in Wistar rats: effect of kindling.

The quantitative autoradiographic [14C]iodoantipyrine technique was applied to the measurement of rates of local cerebral blood flow (LCBF) during audiogenic seizures in Wistar AS rats belonging to a genetic strain selected at the Centre de Neurochimie (Strasbourg, France) for their sensitivity to sound. Seizures were elicited in native rats never exposed to sound (single audiogenic seizures) or in rats previously exposed to 10-40 seizure-inducing sound stimulations until generalization of the seizure to forebrain areas (referred to as "kindled animals"). During single audiogenic seizures, rates of LCBF increased over control values in all areas but the genu of the corpus callosum. The highest increases in LCBF (180-388%) were recorded in the inferior and superior colliculus, reticular formation, monoaminergic cell groupings, especially the substantia nigra, posterior vegetative nuclei, and many thalamic and hypothalamic regions. The lowest increases were seen in forebrain limbic regions and cortical areas. In kindled animals, LCBF rates increased over control levels in 67 areas of the 75 studied. LCBF increases were generally of a lower amplitude in kindled than in naive rats. Differences between the two groups of seizing rats were located mostly in brain-stem regions, mainly the inferior colliculus, reticular formation, substantia nigra, and posterior vegetative nuclei. Conversely, rates of LCBF were similar in forebrain areas of naive and kindled animals. In conclusion, the present data show that there is a good correlation between the structures known to be involved in the expression of audiogenic seizures (inferior colliculus, reticular formation, substantia nigra mainly) and the large increase in LCBF during single audiogenic seizures, while rates of LCBF increase to a lesser extent in forebrain areas not involved in this type of seizures. The circulatory adaptation to kindled seizures is rather a decreased response in brain-stem regions and no change in the forebrain, although the kindling process induces a generalization of the seizure from brain-stem to anterior regions.

Acoustic Stimulation↗
PubMed1995

Effects of pentylenetetrazol-induced status epilepticus on local cerebral blood flow in the developing rat.

The quantitative autoradiographic [14C]-iodoantipyrine technique was applied to measure the effects of a 30-min period of pentylenetetrazol (PTZ)-induced status epilepticus (SE) on local cerebral blood flow (LCBF) in rats 10 (P10), 14 (P14), 17 (P17), and 21 (P21) days after birth. The animals received repetitive, timed injections of subconvulsive doses of PTZ until SE was reached. At P10, SE induced a 32 to 184% increase in the rates of LCBF affecting all structures studied. In P14- and P17 PTZ-treated rats, LCBF values significantly increased in two-thirds of the structures belonging to all systems studied and were not changed by SE in the parietal cortex, dorsal hippocampus, and dentate gyrus. At P21, rates of LCBF were still increased in 48 of the 73 structures studied; however, LCBF values were decreased by SE in most cortical areas, the hippocampus, and the dentate gyrus. CBF and cerebral metabolic rate for glucose (CMRglc) remained coupled in both controls and PTZ-exposed rats. Our results show that changes in LCBF with seizures are age dependent. At the most immature ages, P10 and P14, both LCBF and local CMRglc (LCMRglc) values are largely increased by long-lasting seizures. At P17 and P21, the blood flow response to SE becomes more heterogeneous, with specific decreases in the hippocampus and cortex at P21. The absence of mismatch between LCBF and LCMRglc in PTZ-exposed rats at all ages may explain at least partly why the immature brain is more resistant to seizure-induced brain damage than the adult brain.

Animals↗