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)     

Prefrontal cortex gating of auditory transmission in humans

Middle-latency auditory evoked potentials (MAEPs) were recorded in controls and patients with focal lesions in dorsolateral prefrontal cortex. Unilateral prefrontal lesions increased the amplitude of the Pa component of the MAEP beginning at 25-35 ms poststimulus. The data suggest that prefrontal cortex exerts early inhibitory modulation of input to primary auditory cortex in humans.     

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.     

Differentiation between cortical and subcortical lesions following focal ischemia in cats by multimodality evoked potentials

Regional ischemia was induced in cats by occluding the middle cerebral artery. Evoked and spontaneous electrical activity as well as regional cerebral blood flow (rCBF) were recorded with platinum depth macroelectrodes in three primary cortical areas: the auditory cortex (A, middle ectosylvian gyrus) and the front and hind limb somatosensory cortex (SF and SH, lateral and medial posterior sigmoid gyrus). To distinguish among the various evoked potentials after click, median or tibial nerve stimulation, electrical field interactions had to be eliminated using a multiplex stimulation and analysis system. Spontaneous electrocortical activity was evaluated by power spectral analysis. In all areas, evoked potentials were abolished 10 min after arterial occlusion. However, rCBF behaved differently in these regions: it was severely reduced in A, decreased moderately in SF and remained unchanged in SH. The graded reduction of rCBF in the three cortical areas was related to changes in electrophysiological activity during the first minutes of ischemia. In A, auditory potentials were abolished within 3 min after occlusion, whereas in SH, the decrease of somatosensory responses started after about 5 min. In SF, two components of the EP changes were found: an early decrease immediately and a later decrease about 5 min after occlusion. The different rates of EP impairment possibly correspond to two types of ischemia. The fast EP abolishment seems to be caused by local cortical damage whereas the delayed EP decrease probably reflects impairment of subcortical white matter structures. Thus, this method may be useful for distinguishing between gray and white matter ischemia.     

Age-related changes in human middle latency auditory evoked potentials

We recorded middle latency auditory evoked potentials (MAEPs) in young (20-40 years) and elderly (60-80 years) subjects with normal hearing. The Pa component was prolonged in latency and markedly enhanced in amplitude in the elderly subjects. No changes were found in Na, or in the binaural interaction of the MAEP. Differences in Pa amplitude and latency were not due exclusively to changes in auditory thresholds, since they were not duplicated by changes in stimulus intensity, and persisted when MAEPs from selected young and old subjects were compared at similar SPL levels. The enhancement of Pa amplitude appears to reflect age-related central modifications in auditory processing.     

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.     

The effects of (-)clausenamide on functional recovery in transient focal cerebral ischemia

The effects of (-)clausenamide (clau) on spatial cognitive functions and hippocampal long-term potentiation (LTP) after transient focal cerebral ischemia in rats were investigated. Four weeks after middle cerebral artery occlusion, Morris water maze tasks demonstrated that 2 h of transient forebrain ischemia resulted in a significant decrease in spatial discrimination performance. The escape latency at 4 and 5 days of acquisition trial was lower in the ischemic rats than in sham-operated rats (33.8+/-6.7 sec and 26.8+/-5 sec versus 12.2+/-4.0 sec and 10.4+/-3.6 sec), chronic treatment with clau (10 mg kg(-1) p.o. once daily) significantly improved the impairment (12.4+/-4.1 sec and 15.2+/-3.1 sec). After Morris water maze, the changes in population spike (PS) amplitude were recorded as an index of LTP in the perforant path-dentate gyrus synapses. There was no difference in PS amplitude between the sham-operated and vehicle-treated animals, whereas the fractional increase of PS 20-50 min after tetanus was significantly larger in clau-treated group. Histopathological analysis revealed that clau could protect against neuron loss in the regions of cortex and striatum. In conclusion, these data indicate a beneficial effect of clau for synaptic plasticity and cognitive function impaired by transient focal cerebral ischemia.     

大鼠局灶性脑缺血再灌注后FADD mRNA及其蛋白的表达变化

目的观察大鼠脑缺血再灌注后缺血半暗带皮质内Fas死亡结构域相关蛋白（FADD）mRNA及蛋白的表达变化。方法用半定量的逆转录PCR（RT-PCR）法检测缺血2h再灌注不同时间点缺血半暗带皮质内FADD mRNA的表达,Western blot检测FADD蛋白表达的变化。结果缺血半暗带脑皮质内FADD mRNA及其蛋白的表达于缺血灌注后3h明显升高,再灌注后12h达高峰（P＜0．01）,至再灌注后24h明显下降。结论脑缺血再灌注后缺血半暗带皮质内FADD mRNA及蛋白表达均明显增加,提示FADD可能在脑缺血再灌注损伤中发挥重要作用。     

Microcirculatory derangement and apoptosis in ischemia-reperfusion injury]

This study was undertaken to clarify the involvement of microcirculatory failure and apoptosis in the pathophysiology of cerebral ischemia using ICAM-1 knockout mice (K/O) and BCL-2 transgenic mice, respectively. In both permanent and transient focal ischemia, infarcted size of cerebral cortex in ICAM-1 K/O mice was significantly smaller than that in wild type mice. Microcirucaltaory disturbance in the cerebral cortex after permanent and transient focal ischemia was mitigated in ICAM-1 K/O mice compared with that in wild type mice. However, the number of granulocytes in the infarcted tissue was similar between K/O and wild mice, and neutrophil depletion in K/O mice showed further reduction of cortical infarction after transient focal ischemia. In contrast, neuronal overexpression of BCL-2 in mice showed protective effect on selective neuronal death observed in the hippocampus after transient global forebrain ischemia for 12 min. The present study supported the notion that (1) microcirculatory disturbance mediated through interaction of ICAM-1 and leukocytes played an important role in expansion of cerebral infarction after focal ischemia and (2) apoptosis inhibited in part by overexpression of BCL-2 was involved in selective neuronal vulnerability after transient global ischemia.     

Effects of delayed administration of (-)-epigallocatechin gallate,a green tea polyphenol on the changes in polyamine levels and neuronal damage after transient forebrain ischemia in gerbils

(-)-Epigallocatechin gallate has a potent antioxidant property and can reduce free radical-induced lipid peroxidation as a green tea polyphenol. In previous study, systemic administration of (-)-epigallocatechin gallate immediately after ischemia has been shown to inhibit the hippocampal neuronal damage in the gerbil model of global ischemia. Polyamines are thought to be important in the generation of brain edema and neuronal cell damage associated with various types of excitatory neurotoxicity. We examined the effects of delayed administration of (-)-epigallocatechin gallate on the changes in polyamine levels and neuronal damage after transient global ischemia in gerbils. To produce transient global ischemia, both common carotid arteries were occluded for 3 min with micro-clips. The gerbils were treated with (-)-epigallocatechin gallate (50 mg/kg, i.p.) at 1 or 3 h after ischemia. The polyamines; putrescine, spermidine, and spermine levels were examined using high performance liquid chromatography in the cerebral cortex and hippocampus 24 h after ischemia. Putrescine levels in the cerebral cortex and hippocampus were increased significantly after ischemia and the delayed administrations of (-)-epigallocatechin gallate (1 or 3 h after ischemia) attenuated the increases. Only minor changes were noted in the spermidine and spermine levels after ischemia. In histology, neuronal injuries in the hippocampal CA1 regions were evaluated quantitatively 5 days after ischemia. (-)-Epigallocatechin gallate administered 1 h or 3 after ischemia significantly reduced hippocampal neuronal damage. The present results show that the delayed administrations of (-)-epigallocatechin gallate inhibit the transient global ischemia-induced increase of putrescine levels in the cerebral cortex and hippocampus. (-)-Epigallocatechin gallate is neuroprotective against neuronal damage even when administered up to 3 h after global ischemia. These findings suggest that (-)-epigallocatechin gallate may be promising in the acute treatment of stroke.     

Mild hypothermia on anoxic depolarization and subsequent cortical injury following transient ischemia.

Anoxic depolarization (AD) is one of the major physiological characteristics in the ischemic core. The effect of mild hypothermia on the appearance of AD and subsequent brain injury following profound ischemia is studied to evaluate the protective mechanism of hypothermia against severe ischemia. Sprague-Dawley rats were subjected to transient ischemia by hypotension (50-20 mmHg) and bilateral carotid artery occlusion (BCA-O) for 20 min in normothermia and 30 min in hypothermia. The temperature of body and temporal muscles was maintained at 37.5 degrees C and 36.5 degrees C in normothermia and 33.0 degrees C and 31.0 degrees C in hypothermia, respectively. Recording of the DC potential shift and electrocorticogram and monitoring of the cortical blood flow (CoBF) with a laser Doppler flowmeter were done epidurally on the right parietal cortex. The right parietal cortex pathology was examined 24 h after ischemia in normothermia and after 30 days in hypothermia. AD appeared in all seven normothermic rats with a fall in the CoBF to 9%-10% of the control flow. However, in spite of CoBF reduction to 8%-9% of the control flow, it did not appear in five hypothermic rats. Intra-ischemic CoBF was not statistically different between these two groups. AD appeared with the CoBF decreasing to 4%-5% of the control flow in seven hypothermic rats. Intra-ischemic CoBF in hypothermic rats exhibiting AD was significantly lower than the other two groups. The interval between BCA-O and the appearance of AD in hypothermic rats was 5.1 +/- 0.3 min (mean +/- SE), which was significantly longer than the 2.2 +/- 0.5 min observed in normothermia (p < 0.0005). Of seven normothermic rats exhibiting AD, two died within 24 h and four revealed massive neuronal injury. Of seven hypothermic rats with AD, four died between day 2 and day 13, and one revealed diffuse cerebral infarction. However, no severe ischemic injury or ischemic death was observed in all five hypothermic rats without AD. The incidence of severe neuronal injury or ischemic death was significantly lower in hypothermic rats without AD compared with normothermic rats with AD (p < 0.02) or hypothermic rats with AD (p < 0.05). Although mild hypothermia delays AD, it is suggested that raising the cerebral blood flow threshold for AD appearance has a key role in the hypothermic protection of a severely ischemic area such as the ischemic core.     

Mild hypothermia on anoxic depolarization and subsequent cortical injury following transient ischemia

Abstract

Anoxic depolarization (AD) is one of the major physiological characteristics in the ischemic core. The effect of mild hypothermia on the appearance of AD and subsequent brain injury following profound ischemia is studied to evaluate the protective mechanism of hypothermia against severe ischemia. Sprague-Dawley rats were subjected to transient ischemia by hypotension (50-20 mmHg) and bilateral carotid artery occlusion (BCA-O) for 20 min in normothermia and 30 min in hypothermia. The temperature of body and temporal muscles was maintained at 37.5°C and 36.5°C in normothermia and 33.0°C and 31.0°C in hypothermia, respectively. Recording of the DC potential shift and electrocorticogram and monitoring of the cortical blood flow (CoBF) with a laser Doppler flowmeter were done epidurally on the right parietal cortex. The right parietal cortex pathology was examined 24 h after ischemia in normothermia and after 30 days in hypothermia. AD appeared in all seven normothermic rats with a fall in the CoBF to 9%-10% of the control flow. However, in spite of CoBF reduction to 8%-9% of the control flow, it did not appear in five hypothermic rats. Intra-ischemic CoBF was not statistically different between these two groups. AD appeared with the CoBF decreasing to 4%-5% of the control flow in seven hypothermic rats. Intra-ischemic CoBF in hypothermic rats exhibiting AD was significantly lower than the other two groups. The interval between BCA-O and the appearance of AD in hypothermic rats was 5.1 ± 0.3 min (mean ± SE), which was significantly longer than the 2.2 ± 0.5 min observed in normothermia (p < 0.0005). Of seven normothermic rats exhibiting AD, two died within 24 h and four revealed massive neuronal injury. Of seven hypothermic rats with AD, four died between day 2 and day 13, and one revealed diffuse cerebral infarction. However, no severe ischemic injury or ischemic death was observed in all five hypothermic rats without AD. The incidence of severe neuronal injury or ischemic death was significantly lower in hypothermic rats without AD compared with normothermic rats with AD (p < 0.02) or hypothermic rats with AD (p < 0.05). Although mild hypothermia delays AD, it is suggested that raising the cerebral blood flow threshold for AD appearance has a key role in the hypothermic protection of a severely ischemic area such as the ischemic core. [Neurol Res 1999; 21: 670-676]     

Relationship between the cortical evoked potential and local cortical blood flow following acute middle cerebral artery occlusion in the baboon

In most experimental studies of the effects of ischemia on CNS electrical activity, the ischemia produced has been total. The present experiments, however, were designed to establish quantitatively the changes in electrical activity corresponding to different degrees of cerebral ischemia. The somatosensory evoked potential was measured at various sites on the exposed postcentral gyrus of the anesthetized baboon, and cortical blood flow was assessed in the region of the evoked potential electrode by the highly focal method of hydrogen clearance. The technique of middle cerebral artery occlusion was used to reduce blood flow over the hemisphere. Following occlusion of the artery, the amplitude of the evoked potential typically diminished steadily at a rate depending on the level of residual local blood flow. The rate of depression of the evoked potential amplitude (expressed in units of percent of control per minute) was highly and significantly correlated with the residual flow (r = ?0.95, P < 0.001), which indicated a linear relationship between these variables, the regression line intercepting the flow axis at 15.2 ml/100g/min. The data also strongly suggested a threshold-type relationship between the amplitude of the evoked potential and the local blood flow: If the flow was greater than about 16 ml/100g/min the evoked potential was not affected, but at flows less than about 12 ml/100g/min the evoked potential was abolished.     

短暂脑缺血再灌注后大鼠大脑皮质ATP含量的动态变化

目的　探讨短暂脑缺血再灌注后大鼠大脑皮质ATP含量的动态变化及其与神经功能恢复之间的关系。方法　采用线栓法建立大鼠大脑中动脉闭塞 (MCAO)模型 ,缺血 10min后于再灌注后 0h、1h、3h、6h、12h、2 4h和 72h应用毛细血管电泳法分别测定额顶叶皮质的ATP含量 ,观察其变化规律。结果　缺血 10min后额顶叶皮质ATP的含量急剧下降至对照组的 2 0 %。再灌注后ATP的含量逐渐恢复 ,于再灌注后 1h、3h、6h和 12h恢复至对照组的 70 .5 %、6 5 .7%、84 .8%和 86 .9%。再灌注后 2 4hATP含量再次下降 ,再灌注后2 4h和 72hATP含量仅为对照组的 5 0 % ,与对照组相比差异均有显著性 (P <0 0 1,P <0 0 5 )。缺血 10min再灌注后大鼠肢体功能可逐渐恢复 ,但再灌注后 2 4h起出现不愿活动和进食等表现。结论　短暂脑缺血再灌注后大鼠额顶叶皮质存在细胞能量系统功能恢复滞后的现象。同时 ,随着再灌注的进行还出现了继发性细胞能量系统功能衰竭的现象 ,这可能与脑缺血再灌注后的神经功能延迟恢复有关     

Characteristics of induced spreading depression after transient focal ischemia in the rat

We examined characteristics of spreading depression (SD) induced on the rat cortex 1 day after transient focal ischemia. Male Wistar rats (n=21) were subjected to transient intraluminal thread occlusion of the right middle cerebral artery for 75 min. Twenty-four hours after the reperfusion, cerebral blood flow (CBF) was determined using laser Doppler flowmeter during multiple SDs elicited on both non-stroke (left) and stroke (right) cortex by the topical application of 2 M KCl. We also examined CBF responses before and after the intravenous administration of the nonspecific NOS inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg) in normal and stroke cortex. Animals were divided into two groups; Group 1 (n=12), animals with subcortical infarction and Group 2 (n=9), animals with subcortical plus cortical infarction. There were no differences between non-stroke and stroke sides in the duration or amplitude of the DC potential shifts in either group. The transient CBF hyperemia during SD was not different between non-stroke (372+/-23% of baseline, mean+/-S.E.) and stroke sides (383+/-30%) in Group 1. However, in Group 2, CBF was significantly restricted on the stroke side (192+/-15% vs. non-stroke side, 374+/-33%). In four normal animals without ischemia, there were no differences in CBF response between both sides. L-NAME had no effect on the transient CBF hyperemia during SD in any of the groups. These data suggest that the CBF responses during SD in the peri-infarction area is restricted 1 day after the transient focal ischemia, while CBF responses are intact in normal cortex overlapping a subcortical infarct. Further, our results indicate that nitric oxide does not promote CBF responses during SD in normal cortex or in tissue surrounding infarction.     

Transgenic mice overexpressing truncated trkB neurotrophin receptors in neurons show increased susceptibility to cortical injury after focal cerebral ischemia

It has been suggested that the increased production of endogenous BDNF after brain insults supports the survival of injured neurons and limits the spread of the damage. In order to test this hypothesis experimentally, we have produced transgenic mouse lines that overexpress the dominant-negative truncated splice variant of BDNF receptor trkB (trkB.T1) in postnatal cortical and hippocampal neurons. When these mice were exposed to transient focal cerebral ischemia by occluding the middle cerebral artery for 45 min and the damage was assessed 24 h later, transgenic mice had a significantly larger damage than wild-type littermates in the cerebral cortex (204 +/- 32% of wild-type, P = 0.02), but not in striatum, where the transgene is not expressed. Our results support the notion that endogenously expressed BDNF is neuroprotective and that BDNF signaling may have an important role in preventing brain damage after transient ischemia.     

Auditory evoked potentials from the primary auditory cortex of the cat: topographic and pharmacological studies.

Wave VI (8.4 msec) of the brain-stem auditory evoked potential (BAEP) was maximal in a discrete region of primary auditory cortex (AI) of the anesthetized cat. Wave VI underwent rapid amplitude decrease over millimeter distances in the AI region and followed high stimulation rates. Wave VI did not show intracortical polarity inversion nor was it abolished by epicortical or intracortical GABA administration. The data are compatible with a wave VI source in the terminal axons of the thalamo-cortical radiations. Middle latency auditory responses (MAEPs) generated 10-40 msec after auditory stimulation were also recorded in a circumscribed area of AI. In contrast to wave VI, these primary auditory cortex potentials (Pa 18.3 msec; Nb 31.9 msec) underwent transcortical polarity inversion, correlated with intracortical multi-unit activity in the AI region and were reversibly altered or abolished by epicortical or intracortical GABA administration to the AI region. The data suggest that the Pa and Nb components of the cat MAEP are intracortically generated by neuronal elements in the AI region.     

Therapeutic time window in the penumbra during permanent focal ischemia in rats: changes of free fatty acids and glycerophospholipids

To better define a therapeutic time window for reducing the extent of damage in ischemic penumbra, the time courses of changes in the glycerophospholipid and free fatty acid (FFA) levels were determined in the rat cerebral cortex following induction of the permanent focal ischemia. Focal ischemia induced a biphasic increase in FFA levels in the cerebral cortex, which had been recognized as the ischemic penumbra during the early stages after permanent occlusion of the middle cerebral artery (MCA). The first increase in FFA levels, in which the polyunsaturated fatty acid (PUFA) contained a large number of arachidonic acid (C20:4) molecules, began at 30 min and reached a peak at 1 h, followed by transient return to each sham level 2-6 h after the onset of MCA occlusion. Thereafter, the delayed increase in FFA levels, showing more increases of docosahexaenoic acid (C22:6) molecules than the C20:4 in PUFA compositions, occurred at 24 h. In contrast, the levels of phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2) decreased rapidly at 30 min of ischemia and returned transiently to each sham level at 1-6 h. The levels of phosphatidylcholine (PC) and phosphatidylethanolamine (PE), including polyphosphoinositides (PIPs), began to decrease significantly during the late stages, i.e., 24 h after induction of ischemia. These results suggest that the time-dependent changes in FFA and PIPs levels during the early stages of ischemia (until 6 h after induction) might be an important determinant of the subsequent neuronal death in the ischemic penumbra and that the breakdown of glycerophospholipids in the later stages after the induction of focal ischemia was associated with the development of infarction in the cerebral cortex.     

Generators of middle- and long-latency auditory evoked potentials: implications from studies of patients with bitemporal lesions

We recorded middle- and long-latency auditory evoked potentials (AEPs) in 5 patients (ages 39-72 years) with bilateral lesions of the superior temporal plane. Reconstructions of CT sections revealed that primary auditory cortex had been damaged bilaterally in four of the patients, while in the fifth an extensive left hemisphere lesion included primary auditory cortex while a right hemisphere lesion had damaged anterior auditory association areas but spared primary auditory cortex. Normal middle-latency AEPs (MAEPs) were recorded at the vertex electrode in all of the patients. In 3 of the 5 patients, MAEPs also showed normal coronal scalp distributions and were comparable in amplitude following stimulation of either ear. Two patients showed abnormalities. In one case, Na (latency 17 msec)-Pa (latency 30 msec) amplitudes were reduced over both hemispheres following stimulation of the ear contralateral to the more extensive lesion. In another, with both subcortical and cortical involvement, the Pa was abolished over the hemisphere with the more extensive lesion. Long-latency AEPs were normal in 2 patients whose lesions were largely confined to the superior temporal plane. In 2 patients with lesions extending into the inferior parietal lobe, N1s were abolished bilaterally. In the fifth patient, the N1 showed a slight reduction over the hemisphere with the more extensive lesion. Middle- and long-latency AEPs were differentially affected by some lesions. For example, patients with absent N1s could produce normal Pas. A review of these results and those of previous studies of bitemporal patients suggests that abnormalities in middle- and long-latency AEPs do not necessarily reflect damage to primary auditory cortex per se, but rather the degree of damage to adjacent areas. Abnormalities in MAEPs are associated with subcortical lesions, or cortical lesions extensive enough to denervate thalamic projection nuclei. Abnormalities in the long-latency N1 reflect lesion extension into the multi-modal areas of the inferior parietal lobule. This area appears to exert a critical modulatory influence over N1 generators outside of the superior temporal plane.     

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)