Experimental focal ischemia in cats: changes in multimodality evoked potentials as related to local cerebral blood flow and ischemic brain edema

Somatosensory and auditory evoked cortical potentials (SEP's and AEP's), regional cerebral blood flow, regional brain water content, and alteration of the blood-brain barrier were investigated in 3 cortical areas during permanent and 1- and 2-hour transient occlusion of the left middle cerebral artery and after restoration of blood flow in cats. During occlusion, blood flow in the auditory cortex was severely suppressed. In the fore limb projection area of the somatosensory cortex, blood flow was moderately reduced while it was nearly unaffected in the hind limb projection area. Despite different degrees of ischemia in the 3 cortical areas, all evoked responses were completely abolished within 10 minutes after occlusion. During permanent occlusion, the pattern of blood flow reduction persisted, and all evoked potentials stayed abolished. Recirculation after occlusion restored blood flow rapidly. AEP's recovered poorly after both 1 and 2 hours of ischemia. SEP's regained normal amplitudes soon after recirculation in the group with 1-hour occlusion. After 2 hours of ischemia, the recovery of SEP's was variable but better than that of the AEP's. Remarkable water accumulation was observed in the auditory cortex of all 3 groups and was accompanied in the 2-hour ischemia group by a disruption of the blood-brain barrier. In the 2-hour group, water accumulation was also found in the subcortical white matter radiation, whereas significant changes in regional water content were not observed in the somatosensory areas. The present study indicates that abolition of SEP's during middle cerebral artery occlusion in cats is caused by lesions in the afferent pathway leading to cortical deafferentation rather than by cortical ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic brain ischemia in the monkey assessed by somatosensory evoked potentials and local blood flow measurements

Physiological changes occurring in experimentally induced chronic ischemic areas of the brain in monkeys have been investigated by measuring local cerebral blood flow (lCBF) and recording somatosensory evoked potentials (SEPs) to median nerve stimulation in the cortex and thalamus (VPL). Ischemia was produced by occlusion of the middle cerebral artery (MCA). Its development was followed for weeks in the unanesthetized monkey. SEPs in VPL and cortex were shown to be useful indicators of neuronal activity in the course of brain ischemia. The most reliable parameters were found to be the amplitude of components P10, P12 and P20 of the cortical SEP, generated around the central sulcus. The relationship between the changes in spontaneous recovery of the SEPs, lCBF and behavioral signs, in the course of time, revealed characteristic patterns. Different components of the cortical SEP provide useful information on the localization of the ischemic cortical area. In addition, the amplitude of the VPL SEP may also change significantly after the occlusion of the MCA. Clear evidence for the phenomenon of diaschisis in terms of SEPs, was found in only one animal. An analysis of the relationship between lCBF and the amplitude of the SEPs showed that cortical SEPs could be measured at local CBF levels as low as 15 ml/100 g X min. The relationship between lCBF and cortical SEP amplitude was approximately linear in the range from about 60 ml/100 g X min down to 15 ml/100 g X min.     

Consistency of cerebral blood flow and evoked potential alterations with reversible focal ischemia in cats

To enhance the consistency of the ischemic insult caused by reversible transorbital middle cerebral artery occlusion, we investigated the variability of somatosensory evoked potential amplitudes and regional cerebral blood flow in 26 anesthetized cats using four procedures to induce transient ischemia. These procedures included 60 minutes of left middle cerebral artery occlusion with or without left common carotid artery occlusion and 120 minutes of left middle cerebral artery occlusion with or without bilateral common carotid artery occlusion. Blood flow in the left middle cerebral artery territory was markedly and consistently reduced to less than 20 ml/min/100 g with simultaneous occlusion of the left middle cerebral artery and both common carotid arteries. The standard deviation of blood flow with this procedure (5.4) was less than that with the other three procedures (13-25). The amplitudes of ipsilateral somatosensory evoked potentials were decreased to approximately 20% of control during ischemia with all four procedures. During reperfusion, amplitudes recovered more slowly, to half of control, after both procedures involving 120 minutes of ischemia. After 120 minutes of reperfusion, the range of amplitudes was smallest in the group exposed to middle cerebral artery occlusion with bilateral common carotid artery occlusion. The degree of recovery of the somatosensory evoked potentials correlated with residual blood flow in both the ipsilateral middle cerebral artery territory and in the white matter during ischemia. We conclude that the most consistent model of focal ischemia and reperfusion in cats in which there is partial recovery of somatosensory evoked potentials is occlusion of one middle cerebral artery and both common carotid arteries for 120 minutes.     

Neurofunctional disturbances as related to cortical ischemia and white matter ischemia

We evaluated regional cerebral blood flow (rCBF) by means of hydrogen clearance method as well as [14C]-iodoantipyrine autoradiographic method, cortical auditory evoked potentials (AEP), somatosensory evoked potentials (SEP) induced by forelimb (median nerve) stimulation (SEP-F), and SEP induced by hindlimb (tibial nerve) stimulation (SEP-H) in cats after occlusion of the left middle cerebral artery (MCA) under alpha-chloralose anesthesia. According to the degree of ischemia, the experimental animals were divided into two groups. One was the critical ischemia which was defined as permanent total suppression of AEP, and low residual blood flow in the auditory cortex. And the other was the non-critical ischemia which included transient suppression and spontaneous recovery of the cortical sensory evoked potentials, and high residual blood flow (greater than 15 ml/100 g/min). In one cat with transient suppression of three kinds of sensory evoked potentials, the [14C]-iodoantipyrine (IAP) autoradiograph revealed only a limited ischemic area of subcortical white matter. In the critical ischemia group, ischemia of the primary sensory cortex ranged from the mostly affected primary auditory cortex (supplied by the MCA) to the least affected hindlimb projection area within primary somatosensory cortex (supplied by the ACA). The forelimb projection area of the primary somatosensory cortex (supplied by both ACA and MCA) showed a mild or moderate reduction of rCBF after occlusion. The [14C]-IAP autoradiograph showed severe reduction of the white matter including the somatosensory pathway in the wide range. However, rCBF in the thalamus and hindlimb projection area within somatosensory cortex was almost intact in the cat with ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Somatosensory evoked potentials in rat cerebral cortex before and after middle cerebral artery occlusion

We recorded somatosensory evoked potentials in pentobarbital-anesthetized rats before and after middle cerebral artery occlusion. Trigeminal (vibrissae), median (forelimb), and sciatic (hind limb) nerve stimuli produced consistent, robust, and sharply localized responses in the trigeminal, forelimb, and hind limb regions of the somatosensory cortex of 18 rats. These regions are situated at sequentially greater distances from the center of infarcts produced by middle cerebral artery occlusion. In eight rats, occlusion 1-2 mm below the rhinal fissure abolished somatosensory evoked potentials in all three cortical region within minutes. Positive wavelets preceding the primary cortical response were also diminished by the occlusion, suggesting that ischemia affected the thalamocortical white matter. Four of these eight rats did not show histologically apparent ischemic involvement of the hind limb cortical region at 3 hours after occlusion; sciatic nerve evoked potentials recovered substantially in all four rats, and the amplitudes exceeded baseline (129 +/- 30% at 1 hour, 173 +/- 33% at 3 hours) in three of the four rats. Three of the eight rats did not have gross ischemic involvement of the forelimb cortical region; median nerve evoked potentials recovered fully in all eight rats, but the amplitudes did not exceed baseline. All eight rats had evidence of ischemic damage in the trigeminal cortex; no rat showed full recovery in this region, and all but one had trigeminal evoked potentials that were less than 20% of baseline amplitudes by 3 hours after occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebral blood flows and tissue oxygen levels associated with maintenance of the somatosensory evoked potential and cortical neuronal activity in focal ischemia

The middle cerebral artery was occluded in 18 cats to evaluate the physiological consequences of cerebral blood flow reductions on the somatosensory evoked potential, spontaneous neuronal activity, and oxygen availability in the ipsilateral and contralateral hemispheres. In the ipsilateral ectosylvian gyrus high-grade ischemia was produced as blood flow in the gray matter was reduced from 52.1 +/- 8.6 (mean +/- SE) to 13.3 +/- 9.0 ml/100 g/min and in the white matter from 33.8 +/- 5.6 to 6.1 +/- 6.4 ml/100 g/min. This significant reduction (p less than 0.05) was associated with abolition of the cortical component of the somatosensory evoked potentials. In all animals occlusion resulted in a predictable extended latency change and a variable amplitude response of the cortical component of the contralaterally recorded somatosensory evoked potentials. In 5 animals, oxygen availability was measured and spontaneous neuronal activity in the contralateral hemisphere was recorded. Volume expansion and hemodilution with either dextran or saline infusions elevated cerebral blood flow in the contralateral gray matter significantly (p less than 0.05) compared with the control and clip values. Ipsilateral spontaneous activity stopped within 4-12 minutes of occlusion, while contralateral spike activity persisted at rates at least equal to those recorded immediately following occlusion.     

Functional impairment due to white matter ischemia after middle cerebral artery occlusion in cats

We recorded regional cerebral blood flow, somatosensory evoked potentials, and auditory evoked potentials in the thalamic relay nuclei (ventral posterior lateral nucleus and medial geniculate body) and in the somatosensory and auditory cortices during and after 1 hour of transient left middle cerebral artery occlusion in nine cats. Regional cerebral blood flow was also measured in the thalamocortical tracts of five of these cats. Additionally, the integrity of thalamocortical connections was tested by retrograde labeling of the thalamic nuclei with horseradish peroxidase in eight cats (three of which experienced no ischemia). Regional cerebral blood flow was severely reduced during middle cerebral artery occlusion in the left primary auditory cortex (8.5 ml/100 g/min) and in white matter pathways (6.4-7.6 ml/100 g/min). In contrast, regional cerebral blood flow did not change significantly in the somatosensory cortex or in either thalamic nucleus. Evoked potentials were abolished in both cortices but remained unchanged in the thalamic nuclei. Cortical somatosensory evoked potentials disappeared 5-8 minutes later than auditory evoked potentials. Recirculation after 1 hour of ischemia resulted in rapid and almost complete recovery (94%) of somatosensory evoked potentials and little recovery (18.4%) of auditory evoked potentials. We conclude that in the auditory pathway both cortical and fiber tract ischemia are (perhaps synergistically) responsible for dysfunction, while in the somatosensory cortex evoked potentials are abolished due to white matter ischemia. The delayed disappearance and better recovery of somatosensory than of auditory evoked potentials indicate that ischemic tolerance is higher in fiber tracts than in cortex.     

Cortical deafferentation in cat focal ischemia: disturbance and recovery of sensory functions in cortical areas with different degrees of cerebral blood flow reduction

During and after 15-min occlusion of the middle cerebral artery (MCA) in cats, local CBF and neuronal activity were measured in cortical areas varying in the degree of CBF reduction. In an area within the ischemic center (primary auditory cortex, middle ectosylvian gyrus), CBF was severely suppressed. Click-induced auditory evoked potentials and evoked as well as spontaneous single-unit activity ceased within 1 min after occlusion. Recirculation resulted in a recovery of the different neurophysiological parameters with a time delay ranging from several minutes to 2 h. In two areas surrounding the ischemic focus (a visual area in the marginal gyrus and the forelimb representation area in the primary somatosensory cortex), CBF was reduced but remained above 30 ml/100 g/min during MCA occlusion. Visual flash-induced evoked potentials and somatosensory evoked potentials induced by median nerve electrical stimulation ceased in the corresponding areas with a somewhat slower time course as compared to the auditory responses and they recovered faster after recirculation. In another somatosensory area (hindlimb projection area in the primary somatosensory cortex), CBF stayed nearly at control levels during occlusion. Evoked potentials and single-unit activity induced by tibial nerve electrical stimulation decreased approximately 5 min after occlusion and were abolished approximately 5 min later. At that time, single-unit activity had changed to a nonresponsive pattern but persisted. However, potentials evoked transcallosally by electrical stimulation of the contralateral hemisphere were still recorded. After reopening the MCA, the recovery of neuronal functions was usually complete and occurred within approximately 5 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Failure of the somatosensory evoked potential following middle cerebral artery occlusion and high-grade ischemia in the cat--effects of hemodilution

Acute focal ischemia was created in 10 cats by unilateral retro-orbital middle cerebral artery (MCA) occlusion. Regional cerebral blood flow (CBF) was determined utilizing the hydrogen clearance technique from electrode recordings within the gray matter and white matter of the ectosylvian gyrus of both hemispheres. The somatosensory evoked potential (SSEP) was obtained during contralateral median nerve stimulation. When the MCA was clipped the white and gray matter blood flows in the ipsilateral ectosylvian gyrus were reduced to 14.8 +/- 19.6% and 19.3 +/- 23.7% of control, and the cortical component of the SSEP was abolished. In the contralateral hemisphere an average increase of 3.5% above the control latency and a 10% mean depression in the amplitude of the cortical component of the SSEP were observed following occlusion. CBF in the contralateral hemisphere was unaffected by the MCA clip. Infusion of saline or dextran to lower the hematocrit by approximately 45% did not significantly improve blood flow or restore the SSEP in the hemisphere ipsilateral to the MCA clip. However, significant increases in the contralateral hemisphere gray matter CBF occurred following hemodilution while the latency of the cortical component of the SSEP in this same hemisphere was significantly extended. Elevations in gray and white matter blood flows were achieved in the experimental hemisphere of 3 of 10 cats suggesting a wide range of variation in the collateral circulation.     

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.     

Reproducibility of cerebral cortical infarction in the wistar rat after middle cerebral artery occlusion

Although middle cerebral artery (MCA) occlusion in the rat is often used to study focal cerebral ischemia, the model of ischemia affects the size and reproducibility of infarction. The purpose of this experiment was to methodically examine different preparations to determine the optimum focal cerebral ischemia model to produce a reproducible severe ischemic injury. Eighty-two Wistar rats underwent either 1 hour, 3 hour, or permanent MCA occlusion combined with no, unilateral, or bilateral common carotid artery artery (CCA) occlusion. Three days after ischemia, the animals were prepared for tetrazolium chloride assessment of infarction size. One-hour MCA occlusion produced a coefficient of variation (CV) of 200% with an infarction volume of 20.3+/-10.5 mm(3). Adding unilateral or bilateral CCA occlusion resulted in a CV of 134% and 101%, respectively. Three-hour MCA occlusion combined with bilateral CCA occlusion decreased the CV to 58% with a cortical infarction volume of 82.6+/-12.1 mm(3), P<05, compared with 1-hour MCA occlusion with or without CCA occlusion. Permanent MCA occlusion combined with 3 hours of bilateral CCA occlusion resulted in a CV of 47% with a cortical infarction volume of 89.6+/-16.0 mm(3). These results indicate that 3-hour MCA occlusion combined with bilateral CCA occlusion provide consistently a large infarction volume after temporary focal cerebral ischemia.     

Continuous lidocaine infusion and focal feline cerebral ischemia

We measured somatosensory evoked potentials, infarct size, and cerebral blood flow in 20 cats subjected to occlusion of the middle cerebral artery for 3 hours, followed by an equal period of reperfusion. The cats were randomized into a treatment group that received a continuous infusion of 2 mg/kg lidocaine hydrochloride or a control group that received an equivalent volume of normal saline. All 10 treated cats retained measurable evoked potentials throughout the experiment. In five control cats, evoked potentials disappeared completely at some point during the occlusion (difference between groups significant at p less than 0.001). Mean amplitude of the major cortical wave in the nine treated cats with cerebral infarcts was higher than that of the nine corresponding controls (p less than 0.05). Lidocaine reduced the mean +/- SEM size of the infarcts from 30.1 +/- 6.0% in the control group to 14.7 +/- 4.9% in the treated group (p less than 0.05). As blood flow was reduced in the infarct and peri-infarct zones in the control but not the treated cats, our results suggest that the beneficial effects of lidocaine may be due to preservation of blood flow in the ischemic zone.     

Altered mechanisms of motor-evoked potential generation after transient focal cerebral ischemia in the rat: implications for transcranial magnetic stimulation

We recently demonstrated that a long-lasting transmission defect in cortical synapses caused motor dysfunction after brief middle cerebral artery (MCA) occlusion in the rat despite rapid recovery of axons. In this experimental study, we have examined the impact of differential recovery of synapses and axons on generation of motor-evoked potentials (MEP) recorded from contralateral paralyzed and ipsilateral unaffected muscles, to gain insight into mechanisms of MEPs recorded from stroke patients by transcranial magnetic stimulation (TMS). MEPs generated by focal electrical stimulation of the forelimb area of motor cortex were simultaneously recorded from the brain stem, contra- and ipsilateral forelimb and contralateral hindlimb muscles in rats subjected to transient MCA occlusion. The effect of ischemia on cortical activity and axonal conduction was differentially studied by proximal or distal occlusion of the MCA. Regional cerebral blood flow changes in the forelimb area were monitored by laser-Doppler flowmetry during ischemia and reperfusion. In addition, synaptic transmission within the forelimb area of motor cortex was examined by intracellular and extracellular recording of potentials generated by stimulation of the premotor area. No MEP response was recorded during ischemia. Upon reperfusion: (i) motor axons readily regained their excitability and cortical stimulation caused successive pyramidal volleys (recorded as D waves from the brain stem) and a MEP from contralateral paralytic muscles although synaptic activation of motor pathways was not feasible; (ii) the amplitude of pyramidal volley was increased; (iii) MEPs with a longer latency were recorded from the ipsilateral forelimb. In conclusion, differential recovery of synapses and axons after ischemia may account for some previously unexplained findings (such as preserved MEPs in paralysed muscles) observed in cortical stimulation studies of stroke patients.     

Changes in the somatosensory evoked potential during and immediately following temporary middle cerebral artery occlusion predict somatosensory cortex ischemic lesions in monkeys

Somatosensory evoked potentials (SEP) were recorded during and immediately following temporary middle cerebral artery (MCA) occlusion to determine whether they can be used to predict ischemic lesions to the somatosensory cortex (SI). Twenty-one cynomolgus female monkeys were subjected to four different MCA occlusion durations (15-60 min) during hypotension (45-50 mm Hg mean arterial blood pressure). The amplitude and central conduction time (CCT) of the median nerve SEP were recorded preceding, during, and following occlusion. Two groups were established based on the development of SI ischemic lesions: animals developing SI lesions formed the SI-lesion group (n = 9), and animals without ischemic lesions or with lesions outside the SI cortex formed the SI-spared group (n = 12). Changes in the SEP during and following MCA occlusion under conditions of hypotension were similar to those reported by others. The SEP disappeared in all animals within 15 min of occlusion and reappeared 5 min following reperfusion. Several differences were observed between the SI-lesion and SI-spared groups. The SI-lesion group had a more rapid decrease in SEP amplitude during the first 5 min of occlusion and had smaller SEP amplitudes and longer CCTs during reperfusion. These results suggest that changes in SEP amplitude and latency during and immediately following temporary MCA occlusion predict development of SI ischemic lesions.     

Deafferentation versus cortical ischemia in a rabbit model of middle cerebral artery occlusion

A two-site middle cerebral artery occlusion model in rabbits was developed. Platinum electrodes served for simultaneous recordings of regional cerebral blood flow, auditory evoked potentials, and electroencephalogram in the left and right auditory cortex and in the left medial geniculate body. Auditory evoked potentials and regional cerebral blood flow were also recorded in the subcortical white matter, and regional cerebral blood flow was recorded in the internal capsule. Distal segment occlusion of the middle cerebral artery caused severe cortical ischemia in four of 11 rabbits (Group I), accompanied by abolition of the auditory evoked potential in the left auditory cortex and white matter and severe reduction of the left electrocorticogram. Deep subcortical regions were affected either little or not at all. In the remaining seven rabbits (Group II) with only mild disturbance of cortical perfusion after distal middle cerebral artery occlusion, additional clamping of the proximal middle cerebral artery stem reduced thalamocortical tract blood flow and abolished cortical auditory evoked potentials. Spontaneous electrocorticogram was less affected in Group II than in Group I; thalamic regional cerebral blood flow and auditory evoked potentials were not altered. Histologically, ischemic lesions predominated in the cortex of Group I and in the subcortical structures of Group II rabbits. While correlated reductions in regional cerebral blood flow and auditory evoked potentials indicate effective cortical ischemia, the impairment of auditory evoked potentials in Group II rabbits must be due to cortical deafferentation by ischemia in the afferent tract. This model permits the investigation of the effects of predominantly cortical or subcortical ischemia in one functional system.     

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.     

Anesthetic modulation of cerebral hemodynamic and evoked responses to transient middle cerebral artery occlusion in cats

We measured cerebral blood flow and somatosensory evoked potentials during transient focal cerebral ischemia in cats to compare the effects of four commonly used anesthetic regimens: ketamine/fentanyl/N2O (fentanyl), pentobarbital, ketamine/alpha-chloralose (alpha-chloralose), and ketamine/halothane/N2O (halothane). Six cats in each group were subjected to 60 minutes of left middle cerebral artery occlusion followed by 120 minutes of reperfusion. Although the amplitude of the initial somatosensory evoked potential wave complex was highest in the alpha-chloralose group (58.6 +/- 16.5 microV) and smallest in the halothane group (27.5 +/- 5.7 microV), amplitude fell by 75% in all groups upon occlusion. Baseline cerebral blood flow varied substantially between groups (e.g., in the right intersylvian gyrus: fentanyl, 96 +/- 12; pentobarbital, 30 +/- 5; alpha-chloralose, 24 +/- 3; and halothane, 76 +/- 11 ml/min/100 g). Occlusion decreased cerebral blood flow to subcortical (e.g., left caudate) structures in all groups (fentanyl, 29 +/- 11%; pentobabital, 45 +/- 12%; alpha-chloralose, 27 +/- 13%; and halothane, 18 +/- 5% of baseline). Postischemic hyperemia occurred in the cortical regions of cats anesthetized with pentobarbital or alpha-chloralose that had reduced cerebral blood flows during occlusion but not in cats anesthetized with fentanyl (cerebral blood flow during occlusion not different from that of cats anesthetized with pentobarbital or alpha-chloralose) or halothane. After 120 minutes of reperfusion, cerebral blood flow had returned to baseline values in all groups. Recovery of cerebral blood flow and somatosensory evoked potential amplitude at that time did not differ among groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

大鼠局灶性脑缺血后CPP32和P53蛋白的表达

目的　探讨大鼠脑缺血后神经元损害过程中CPP32和P5 3蛋白表达的变化。方法　建立大鼠大脑中动脉闭塞 (MCAO 2h)模型 ,采用免疫组化方法观察CPP32和P5 3蛋白在大鼠脑缺血后不同时间的动态变化。结果　CPP32蛋白在脑缺血再灌注 2 2h和 4 6h ,阳性表达最明显。而P5 3在脑缺血再灌注 2 2h阳性表达最明显 ,并持续至再灌注 70h。阳性表达主要位于神经元严重受损的缺血区内。结论　CPP32和P5 3蛋白表达与脑缺血后神经细胞死亡关系密切。     

Acute improvement in histological outcome by MK-801 following focal cerebral ischemia and reperfusion in the cat independent of blood flow changes.

The present study reports on the acute effects of MK-801 on the histopathological outcome and blood flow changes during focal cerebral ischemia and reperfusion. In addition, acute changes in the EEG and blood pressure are also reported. In 16 halothane-anesthetized cats, the left middle cerebral artery (MCA) was occluded for 2 h followed by 4 h of reperfusion. Thirty minutes after the onset of ischemia, eight animals were treated with 1 mg/kg of MK-801, while eight animals received saline. Blood flow from the peripheral MCA territory was measured with H2 clearance. There was a comparable reduction in blood flow (down to 20% of control) in the ischemic gyri of the two groups followed by a partial recovery after recirculation. There was a similar decrease in the EEG amplitude over the ischemic central MCA territory in the treated and the untreated group. Treatment with MK-801 induced a burst suppression in the EEG and a transient drop (11.4 +/- 6.5 mm Hg) in the mean arterial pressure. The volume of early ischemic damage decreased by one-third in the MK-801-treated group compared to the untreated one, both in the total hemisphere (from 29 +/- 10 to 20 +/- 5%) and in the hemispheric cortex (range 36 +/- 8 to 24 +/- 13%). A major fraction of this improvement was localized to the middle and posterior parietal (mainly perifocal) regions of the MCA territory. These results show that in our model, MK-801 improves histopathological outcome despite the lack of apparent effect on the cortical blood flow, and an adverse effect on the systemic blood pressure. This is the first report that describes data on a reproducible model of reperfusion after temporary occlusion of the MCA in a cat, extending the findings of the Glasgow group, who observed similar neuroprotection in models of permanent MCA occlusion.     

大鼠大脑中动脉缺血/再灌注模型中Caspase-3的表达

目的 研究Caspase-3在缺血性脑损伤中的作用，进一步探讨缺血性脑血管病的分子机制。方法 用Belayev改良的Longa线栓法制备大鼠局灶性大脑中动脉(MCA)缺血／再灌注模型，TTC染色观察梗死灶的形成，分别用原位杂交及免疫组化技术检测鼠脑中Caspase-3 mRNA与活性蛋白的表达。结果 缺血2小时再灌注24小时，TTC染色见明显的梗死灶形成，正常脑组织、假手术组及MCAO缺血对侧脑中有少量的Caspase-3 mRNA表达，但活性蛋白几无表达；再灌注24小时后，缺血侧脑中Caspase-3 mRNA表达明显增强，蛋白质活化增多，再灌注48小时进一步增加。结论 细胞凋亡机制参与了缺血后迟发性神经元死亡，Caspase-3在其中起重要作用。