Neural damage in the rat thalamus after cortical infarcts.

Histopathologic changes in the thalamus of 23 rats after somatosensory cortical infarction produced by middle cerebral artery occlusion were examined using the Fink-Heimer silver staining method, immunohistochemistry with antibodies against glial fibrillary acidic protein and laminin, and conventional stains. Middle cerebral artery occlusion produced cortical infarcts in the lateral parietal region, with variable involvement of the frontoparietal parasagittal sensorimotor cortex. Within 3 days after occlusion, massive terminal degeneration but no neuronal changes were apparent in the ipsilateral thalamus. By 1 week after occlusion, abnormal neurons with darkly stained, shrunken nuclei and atrophic perikarya were present in the ipsilateral thalamic nuclei. These neurons were densely argyrophilic in Fink-Heimer sections. Rats with small lateral parietal cortical lesions had degenerating neurons limited to the medial ventroposteromedial nucleus. Large lesions involving the parasagittal sensorimotor cortex resulted in widespread neuronal damage in the ventroposteromedial, ventroposterolateral, intralaminar, and posterior nuclear regions but nowhere else. Immunoreactivity to laminin antibody decreased, and astrocytic proliferation was abundant in affected thalamic areas. These findings are consistent with retrograde neuronal degeneration due to thalamocortical fiber damage in ischemic cortical regions. Such lesions remote from the infarct may influence functional recovery in patients with stroke.     

Cholinergic deafferentation after focal cerebral infarct in rats

BACKGROUND AND PURPOSE: For a better understanding of neuronal network disturbances after stroke, we investigated the changes in the cholinergic system after experimental focal infarct. METHODS: We quantitatively evaluated the highly sensitive acetylcholinesterase histochemistry and local glucose utilization 7 days after left middle cerebral artery occlusion in Wistar rats. RESULTS: In all rats with occlusion, the ipsilateral frontal cortex and the nucleus basalis Meynert developed no infarct, whereas the subcortical striatum did. In the frontal cortex on the occlusion side, the acetylcholinesterase-positive fiber density was significantly (p less than 0.05) reduced; a computer-assisted image-analyzing system quantified approximately 1.0 m/mm3 brain cortex acetylcholinesterase-positive fibers in the ipsilateral frontal cortex layers II-IV and approximately 9.7 m/mm3 brain cortex acetylcholinesterase-positive fibers in the contralateral frontal cortex layers II-IV. Local glucose utilization was also significantly (p less than 0.05) decreased in the ipsilateral frontal cortex compared to the contralateral side and sham-operated animals. CONCLUSIONS: These results suggest that functional disturbances and disruption of the cholinergic pathway between the frontal cortex and the nucleus basalis Meynert occur after middle cerebral artery occlusion in rats.     

Exo-focal postischemic neuronal death in the rat brain

We describe delayed neuronal damage in ipsilateral areas remote from the ischemic area of rat brain after transient focal ischemia induced by embolization of the right middle cerebral artery (MCA). After 15, 30, 60 and 90 min of MCA occlusion, recirculation was achieved by removal of the embolus. Chronological changes in the distribution of the neuronal damage were determined by using the 45Ca autoradiographic technique and the histological method, and the mechanism involved was investigated by measuring local cerebral glucose metabolism. Depending on the duration of ischemia, 45Ca accumulation extended to the lateral segment of the caudate putamen and to the cerebral cortex, both supplied by the occluded MCA. Moreover, 3 days after ischemic insult, 45Ca had accumulated in the ipsilateral substantia nigra and ventral posterior nucleus of the thalamus. Histological examination revealed that the neurons in both areas suffered damage and were selectively reduced in number. Cerebral glucose utilization decreased in the thalamus, but increased approximately 30% (P less than 0.01) in the substantia nigra compared with the value in the corresponding contralateral area. Both areas lie outside the ischemic area, but have transsynaptic connections with the ischemic focus. Based on the present study, we suggest that the mechanisms of delayed neuronal death in these two remote areas may not be identical, but that this phenomenon may be caused by a transsynaptic process associated with the ischemic focus.     

Selective cortical neuronal damage after middle cerebral artery occlusion in rats

We studied histopathologic changes in cerebral cortex of 20 rats after middle cerebral artery occlusion by using the Fink-Heimer suppressive silver impregnation method and conventional stains. At 6 hours after occlusion, Fink-Heimer-stained sections revealed abundant coarsely granular, intensely argyrophilic neurons in the ischemic cortex. These distinctive argyrophilic neurons could be clearly differentiated from neurons that suffered postmortem changes; argyrophilic neurons were present in all layers of the lateral parietal cortex but in only the superficial cortical layers II and III in the parasagittal area of the frontoparietal cortex and the temporo-occipital area. At 24 hours after occlusion as the ischemic region progressed to pannecrosis, argyrophilic neurons were still evident in peri-infarct regions, with more prominent neuritic silver deposits but no changes in number or spatial distribution. Over 2-7 days, the argyrophilic neurons gradually disappeared while many fine silver-impregnated degenerating terminals appeared in the peri-infarct regions. At 3-6 weeks after occlusion, no more argyrophilic neurons were seen in the cortex although degenerating axons were still present in the deep white matter. Our results indicate selective neuronal damage in the superficial cortical layers and massive axonal degeneration in the cerebrum surrounding infarcts. The neuronal damage does not appear to progress beyond 6 hours after middle cerebral artery occlusion. The Fink-Heimer method has many advantages over existing conventional stains for documenting selective neuronal damage in focal cerebral ischemia.     

Ischemic axonal injury and its recovery after focal cerebral ischemia

After focal cerebral infarction by occluding the middle cerebral artery (MCA) of the rat, the neuronal death occurred in the ipsilateral thalamic neurons, because axons of the thalamic neurons were injured by infarction and retrograde degeneration occurred in the thalamic neurons. However, cortical neurons adjacent to the infarction survived despite their axons injured by ischemia. We employed immunohistochemical staining for 200 kilodalton (kD) neurofilament (NF), in order to study those responses of cortical and thalamic neurons against axonal injury caused by focal cerebral infarction. In the sham operated rats the immunoreactivity to the anti-200 kD NF antibody was only detected in the axon but not in the cell bodies and dendrites. At 3 days after MCA occlusion, axonal swelling proximal to the site of ischemic injury was found in the caudoputamen and internal capsule of the ipsilateral side. At 7 days after occlusion, cell bodies and dendrites of the neurons in the ipsilateral cortex and thalamus were strongly stained with anti-NF antibodies. At 2 weeks after occlusion these responses disappeared in the cortex, but lasted in the thalamus. These phenomena are caused by stasis of the slow axonal transport, because the NF is transported by slow axonal transport. In the cortical neurons impairment of slow axonal transport recovered in the early phase after injury, but in the thalamic neurons the impairment prolonged up to 3 weeks after occlusion. The early recovery of axonal transport from ischemia seemed to be essential for survival of neurons after ischemic axonal injury.     

Autoradiographic determination of cerebral glucose content, blood flow, and glucose utilization in focal ischemia of the rat brain: influence of the plasma glucose concentration

Focal cerebral ischemia was produced by occlusion of the middle cerebral artery in rats. Cerebral blood flow measured with [14C]iodoantipyrine was severely reduced in the lateral portion of neostriatum. This area of dense ischemia was sharply demarcated against the surroundings. The adjacent cortex was perfused at one-third of normal, whereas blood flow in the medial neostriatum was only slightly reduced. This pattern of perfusion was independent of the plasma glucose concentration of the animal. In contrast, the glucose utilization calculated from the 2-[3H]deoxyglucose accumulation depended on the plasma glucose concentration. Enhanced glucose utilization was evident in the border areas surrounding the ischemic focus in normoglycemic animals. Neither acutely nor chronically diabetic animals had such an increase of metabolism in the borderzone. Moderately hyperglycemic rats had a narrow rim of enhanced glucose utilization immediately surrounding the ischemic core, whereas animals with plasma glucose values above 22 mmol/L had no such rim. In mild hypoglycemia (2-4 mmol/L), the glucose utilization was slightly enhanced in the border areas, but during severe hypoglycemia (less than 2.5 mmol/L), the glucose utilization declined gradually toward the ischemic core. Glucose content, and thereby the lumped constant (measured by 3-0-[14C]methylglucose) showed little regional variation, except in the ischemic core. These findings indicate that blood flow alterations after occlusion of the middle cerebral artery in rats are not influenced by the plasma glucose utilizations. In contrast, glucose utilization depends on a combination of plasma glucose concentration and blood flow instead of blood flow per se.     

Acute thrombotic infarction suppresses metabolic activation of ipsilateral somatosensory cortex: evidence for functional diaschisis

To study the effects of focal infarction on the capacity for functional activation of an ipsilateral somatosensory system remote from the lesion, we produced a small thrombotic infarct in the left frontal pole of male Wistar rats by a photochemical method. Five days later, the awake, restrained rats received tactile stimulation of the large whiskers (vibrissae) of the right side of the face, while a double-label 14C-autoradiographic study of local CMRglc (lCMRglc) and local CBF (lCBF) was performed. Unlesioned and unstimulated animals served as controls. In rats without frontal infarct, vibrissae stimulation led to activation of lCMRglc in the three synaptic relay stations of the barrel-field pathway (ipsilateral trigeminal medullary nucleus, contralateral ventrobasal thalamus, and contralateral barrel-field cortex). The mean increment in lCMRglc was 42% in lamina IV of barrel-field cortex and 49% in ventrobasal thalamus. Normalized lCBF tended to increase in superficial cortical laminae. In unstimulated animals with frontal infarct, lCMRglc was reduced by 20-30% throughout the ipsilateral barrel-field cortex as well as other ipsilateral cortical regions, but not in ventrobasal thalamus or other subcortical areas. In animals with frontal infarct subjected to contralateral vibrissae stimulation, a remarkable suppression of activation was observed throughout the barrel-field cortex so that left-less-than-right hemispheral lCMRglc asymmetry persisted despite stimulation. The ventrobasal thalamus, similarly, failed to increment its lCMRglc with vibrissae stimulation, whereas activation of the trigeminal nucleus was not suppressed. Similar trends were observed in the normalized lCBF data. These observations, which establish that a small frontal infarct is capable of suppressing normal physiological activation in remote ipsilateral brain structures, may have important implications with respect to suppression and recovery of function in human ischemic stroke.     

Progressive shrinkage of the thalamus following middle cerebral artery occlusion in rats

Permanent middle cerebral artery occlusion in rats results in infarction in the ipsilateral cortex and caudate nucleus-putamen. In this ischemia model, severe shrinkage of the ipsilateral half of the thalamus was observed several months after surgery. We examined the serial profile of this phenomenon in 40 rats at intervals from 2 weeks to 6 months after the operation. The area of the ipsilateral half of the thalamus as a percentage of the area of the contralateral half was 87% at 2 weeks, 77% at 1 month, 54% at 3 months, and 54% at 6 months. Such severe morphologic change distant from the original ischemic focus has not been reported in models of experimental focal ischemia. Retrograde degeneration is thought to play an important role in this phenomenon.     

Neurologic and neuropathologic outcome after middle cerebral artery occlusion in rats

Focal cerebral ischemia was produced in 45 rats by occlusion of the left middle cerebral artery. Groups of rats were investigated over a long period after occlusion, that is, from a few hours to 42 days after the production of focal ischemia. Light microscopy showed infarcts in the frontoparietal cortex and the lateral caudoputamen. The ischemic changes closely resembled those found in ischemic infarcts in humans and followed a similar pattern over time. Measurements of the sizes of the infarct, the ipsilateral (operated) hemisphere, and the contralateral hemisphere from camera lucida drawings revealed that the infarct size changed with time after occlusion. Rats killed during the first 7 days (acute phase) had the largest infarcts; in rats killed thereafter, the infarct size diminished. The size of the ipsilateral hemisphere also changed with time; during the first 7 days after occlusion this hemisphere was swollen and larger than the contralateral hemisphere. We suggest that these acute changes are caused by cerebral edema. After the first 7 days, enlargement of the ipsilateral hemisphere gave way to a significant reduction in the size of both the ipsilateral hemisphere and the infarct. We believe that the major reasons for this shift in size are resorption of fluid together with diminished production of edema and elimination of dead cells by macrophages. We suggest that the amount of tissue loss (i.e., the degree of atrophy and the remaining infarct "scar") found 21-42 days after occlusion (during the late phase) is a measure of the total amount of tissue that succumbed as a consequence of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

ALS-linked Cu/Zn-SOD mutation impairs cerebral synaptic glucose and glutamate transport and exacerbates ischemic brain injury.

Although degeneration of lower motor neurons is the most striking abnormality in amyotrophic lateral sclerosis (ALS), more subtle alterations may occur in the brain. Mutations in copper/zinc superoxide dismutase (Cu/Zn-SOD) are responsible for some cases of inherited ALS, and expression of mutant Cu/Zn-SOD in transgenic mice results in progressive motor neuron loss and a clinical phenotype similar to that of ALS patients. It is now reported that Cu/Zn-SOD mutant mice exhibit increased vulnerability to focal ischemic brain injury after transient occlusion of the middle cerebral artery. Levels of glucose and glutamate transport in cerebral cortex synaptic terminals were markedly decreased, and levels of membrane lipid peroxidation were increased in Cu/Zn-SOD mutant mice compared to nontransgenic mice. These findings demonstrate that mutant Cu/Zn-SOD may endanger brain neurons by a mechanism involving impairment of glucose and glutamate transporters. Moreover, our data demonstrate a direct adverse effect of the mutant enzyme on synaptic function.     

Hyperglycaemia protects against neuronal injury around experimental brain infarcts

Regional glucose utilization was measured in the rat brain after occlusion of the middle cerebral artery. Normoglycaemic rat had increased glucose use in the cerebral cortex adjacent to the infarct. A fraction of the nerve cells were irreversibly injured in this region. In hyperglycaemic rats, the glucose metabolism remained normal and no nerve cell loss was found around the infarct. The findings indicate that hyperglycaemia protects against nerve cell injury in the areas next to experimental brain infarcts.     

Functional changes in thalamic relay neurons after focal cerebral infarct: a study of unit recordings from VPL neurons after MCA occlusion in rats.

We evaluated neuronal and histological changes of thalamic neurons 1, 4, 7, and 14 days after middle cerebral artery (MCA) occlusion in rats. After the somatosensory evoked potentials (SEPs) were measured from the cerebral cortex, the thalamic relay neuronal activities were recorded with a glass microelectrode following repetitive electrical stimulation of the contralateral forepaw at frequencies ranging from 1 to 50 Hz. In approximately 95% of the occluded rats, the ipsilateral somatosensory cortex and/or the subcortical somatosensory pathway developed infarct, resulting in SEP loss. We evaluated unit data from rats with abolished SEPs. The average firing rate of the nucleus ventralis posterolateralis (VPL) neurons in response to 25 stimulations at 30 Hz was significantly reduced to 0.1 spike/stimulus 1 day after MCA occlusion. In sham-operated rats, the same stimulation produced 0.7 spike/stimulus. The firing rate recovered to 0.4 spike/stimulus at 30-Hz stimulation 4 and 7 days after occlusion. This was followed by resuppression (0.1 spike/stimulus) 14 days after occlusion. Histological study revealed some abnormal neurons in the ipsilateral thalamus 7 days after occlusion. We were unable to find normal-shaped neurons in the VPL 14 days after occlusion. The present study demonstrates that cortical infarct produces functional and morphologic changes that gradually and progressively affect the ipsilateral thalamus, although incomplete transient recovery of somatosensory transmission may occur.     

Intrinsic circuitry involving the local axon collaterals of corticothalamic projection cells in mouse SmI cortex

The objective of this study was to identify the components involved in a local synaptic circuit in the mouse cerebral cortex. The local axon collaterals of corticothalamic (CT) projection cells in the posteromedial barrel subfield area of primary somatosensory cortex were labeled by the retrograde transport of horseradish peroxidase injected into the ipsilateral thalamus. Thalamocortical (TC) axon terminals in the same region of cortex were labeled by lesion induced degeneration. CT axon terminals synapsed preferentially with dendritic shafts, whereas TC axon terminals synapsed mainly with dendritic spines. Some dendrites received both CT and TC synapses. Dendrites were interpreted to belong to nonspiny multipolar cells. These results indicate that a reciprocal synaptic relationship exists in the cortex between nonspiny multipolar cells and CT projection cells. Both CT projection cells and nonspiny multipolar neurons have been shown previously to receive TC synapses (White and Hersh: J. Neurocytol. 11:137-157, '82; White, Benshalom, and Hersch: J. Comp. Neurol. 229:311-320, '84). These findings imply that a triadic relationship involving afferent input and populations of CT projection and intrinsic neurons is a basic feature of the synaptic organization of the cerebral cortex.     

大鼠大脑皮层梗死后丘脑继发性轴突变性

目的 探讨高血压大鼠大脑皮层梗死同侧丘脑腹后核（ventroposterior nucleus of the thalamus,VPN）继发性轴突变性的病理过程。方法 采用易卒中型肾血管性高血压大鼠（stroke-prone renovascular hypertensive rats,RHRSP）模型制备右侧大脑中动脉皮层支闭塞（middle cerebral artery occlusion,MCAO）模型,作为MCAO组。RHRSP模型仅暴露而不凝闭右侧大脑中动脉皮层支（middle cerebral artery,MCA）,作为假手术组。健康配对的成年大鼠,作为正常对照组。上述3组动物分别在术后1、2、4周3个时间点,行Bielschowsky氏嗜银染色及免疫组织化学染色检测梗死同侧丘脑腹后核βA4淀粉样前体蛋白（amyloid βA4 precursor protein,APP）、生长相关蛋白43（growth associated protein-43,GAP-43）和微管相关蛋白2（microtubule associated protein-2,MAP-2）的表达水平。结果 与同期假手术组相比,在梗死同侧丘脑腹后核,缺血4周时检测到嗜银染色的纤维束明显减少（P <0.05）;APP蛋白在缺血1周时表达开始增强并逐渐增高（P <0.05）,GAP-43蛋白、MAP-2蛋白的表达水平在缺血1～2周开始下降（P <0.05）并持续降低（P <0.05）。结论 轴突标志性蛋白的免疫组织化学检测方法敏感性高、能早期发现丘脑轴突的病理改变,与传统的嗜银染色方法结合,能较全面地评价VPN轴突变性的病理过程。本实验发现梗死同侧VPN的轴突变性是一个慢性进展性的过程。     

Differences in the extent of primary ischemic damage between middle cerebral artery coagulation and intraluminal occlusion models.

The authors studied the differences between heat-shock/stress protein 70 (hsp70) gene expression and protein synthesis in the unilateral middle cerebral artery (MCA) microsurgical direct occlusion (Tamura's) model and the unilateral intraluminal occlusion model. In Tamura's model, expression of hsp70 mRNA and HSP70 protein and decreased protein synthesis were detected in the ischemic areas, including the ipsilateral cortex and caudate. These phenomena, however, were not observed in the areas outside the MCA territory, including the ipsilateral thalamus, hippocampus, and substantia nigra. These results were consistent among the experimental rats. In the intraluminal occlusion model, however, induction of both hsp70 mRNA and HSP70 protein and impairment of protein synthesis were noted in the areas outside the MCA territory, including the ipsilateral thalamus, hypothalamus, hippocampus, and substantia nigra, as well as in the MCA territory, including the ipsilateral cortex and caudate. These results were not consistent among the experimental rats. These different results might be due to widespread damage resulting from internal carotid artery (ICA) occlusion in the intraluminal occlusion model. Accordingly, the authors suggest that this model be called an ICA occlusion model, rather than a pure MCA occlusion model.     

Pure amnesia after unilateral left polar thalamic infarct: topographic and sequential neuropsychological and metabolic (PET) correlations.

A 54-year-old patient who had an isolated small polar thalamic infarct and acute global amnesia with slight frontal type dysfunction but without other neurological dysfunction was studied. Memory improved partially within 8 months. At all stages the impairment was more severe for verbal than non-verbal memory. Autobiographic recollections and newly acquired information tended to be disorganised with respect to temporal order. Procedural memory was unaffected. Both emotional involvement and pleasure in reading were lost. On MRI, the infarct was limited to the left anterior thalamic nuclei and the adjacent mamillothalamic tract. The regional cerebral metabolic rate of glucose (measured with PET) was decreased on the left in the thalamus, amygdala, and posterior cingulate cortex 2 weeks after the infarct, and in the thalamus and posterior cingulate cortex 9 months later. These findings stress the specific role of the left anterior thalamic region in memory and confirm that longlasting amnesia from a thalamic lesion can occur without significant structural damage to the dorsomedial nucleus. Furthermore, they suggest that the anterior thalamic nuclei and possibly their connections with the posterior cingulate cortex play a role in emotional involvement linked to ipsilateral hemispheric functions.     

Effects of cerebrovascular autoregulation and CO2 reactivity in experimental localized brainstem infarction

Using the previously reported method of experimental localized brainstem infarct in dogs, we designed this study to elucidate sequential changes of regional cerebral blood flow (rCBF) in three separate regions of the central nervous system: the cerebral cortex, thalamus, and midbrain. The data obtained were referred to in subsequent investigations of cerebrovascular autoregulation and vasomotor reactivity to CO2. Localized brainstem infarct was produced by permanently occluding the perforators of the posterior cerebral arteries between the bilateral origins of the posterior communicating arteries. The hydrogen clearance method was applied to measure rCBF. Cerebrovascular autoregulation and CO2 reactivity were assessed in three regions 1, 3, and 5 h after vascular occlusion, respectively. Vascular occlusion resulted in a decrease of rCBF that was 65% in the midbrain and close to 30%-40% in the thalamus. However, no significant change was seen in the cerebral cortex even 5 h after vascular occlusion. Induced hypertension impaired autoregulation in the thalamus, while it was preserved in the cerebral cortex. Induced hypotension did not alter autoregulation in any of the three regions. A marked loss of CO2 reactivity was observed in the ischemic brainstem, although it was well preserved in the cerebral cortex. The results suggest that noradrenergic fibers originating from the cervical sympathetic ganglia play a main role in the cerebrovascular autoregulation in the cerebral cortex, while noradrenergic fibers possibly originating from the autonomic centers in the brainstem are responsible in the thalamus; that the noradrenergic neuron probably is not involved in the maintenance of cerebral blood flow during hypotension; and that the effect of CO2 is mediated by its direct effect on the arteriolar wall in the central nervous system.     

Multi-focal delayed neuronal damage after transient regional ischemia--mechanism of vascular dementia

We describe multi-focal delayed neuronal death of rat brain after transient regional ischemia induced by embolization of the right middle cerebral artery (MCA). After sixty minutes of MCA occlusion, recirculation was achieved by removal of the embolus. Chronological changes in the distribution of the neuronal damage were determined by using the 45Ca autoradiographic technique and the histological examination. Sixty minutes after MCA occlusion, 45Ca accumulation extended to the lateral segment of the caudate putamen and the cerebral cortex supplied by the occluded MCA. Moreover, three days after ischemic insult, 45Ca had accumulated in the ipsilateral thalamus and substantia nigra. Histological examination revealed that the neurons in both area suffered damage and were selectively reduced in number. Both areas lie outside the ischemic area, but have transsynaptic connections with the ischemic focus. We suggest that the postischemic delayed neuronal death in exo-focal remote areas may be caused by a transsynaptic process associated with the infarcted areas and that these delayed multi-focal brain damage may exacerbate clinical symptoms in the chronic stage of stroke.     

Immunohistochemical investigation of ischemic and postischemic damage after bilateral carotid occlusion in gerbils

We investigated progression and recovery of neuronal damage during and after global cerebral ischemia in gerbils after bilateral occlusion of the common carotid arteries, using the immunohistochemical method (reaction for tubulin and creatine kinase BB-isoenzyme). The earliest, but reversible, ischemic lesions occurred after 3 minutes' ischemia in the subiculum-CA1 and CA2 regions of the hippocampus. The lesions became irreversible after 4 minutes' ischemia. The ischemic and postischemic lesions in the cerebral cortex, thalamus, and caudoputamen were partially or completely reversible if the ischemic period was 5 minutes, whereas delayed degeneration occurred in the pyramidal cells of the medial CA1 region after reperfusion for 48 hours (delayed neuronal death). After 10 minutes' ischemia and subsequent reperfusion, delayed neuronal death extended from the medial to the lateral CA1 region; the ischemic and postischemic lesions in the cerebral cortex, thalamus, and caudoputamen also expanded during reperfusion. Our investigation demonstrates that selective vulnerability existed in global cerebral ischemia as in incomplete or regional ischemia and suggests that neurons in many areas of the brain possessed the potential for recovery, progressive deterioration, and even delayed neuronal death depending on the severity and duration of cerebral ischemia.     

Up-regulation of c-myc gene expression following focal ischemia in the rat brain

Abstract

Changes in gene expression including that ofc-fos occur following cerebral ischemia. Proto-oncogenes c- myc and s-myc and oncosuppressor gene p53 are known to induce apoptosis in some types of cells, whereas proto-oncogene bcl-2 inhibits apoptosis. Possible induction of mRNAs for c-myc, N-myc, s-myc, c-fos, p53 and bcl-2 was examined following focal ischemia in the rat anterior cortex, hippocampus, thalamus and cerebellum by Northern blot analysis. Animals were decapitated 1, 2, 6, 12, and 24 hours following the left middle cerebral artery (MCA) occlusion. In sham-operated control rats, the mRNAs for c- myc, N-myc, c-fos and p53 were present in the anterior cortex, hippocampus; thalamus on both sides, and in the cerebellum, whereas those for s-myc and bcl-2 were not The c-myc gene expression was rapidly and markedly induced by the MCA occlusion in the ipsilateral anterior cortex, hippocampus and thalamus in a time-dependent manner. In these regions, the c-fos gene expression was also induced as early as 1 hour after the MCA occlusion. The p-53 mRNA was induced in the ipsilateral hippocampus at 24 hours after MCA occlusion. In contrast, mRNAs for N-myc, s-myc and bcl-2 were not induced following MCA occlusion. These results indicate a possibility that high-level expression of the c-myc gene may be involved in the ischemic cellular events including apoptosis. [Neurol Res 1996; 18: 559-563]