Substantia nigra damage induced by ischemia in hyperglycemic rats

Inamura, Keiji; Olsson, Yngve; Siesjö, Bo K.

doi:10.1007/bf00687073

Cited by 36 publications

(14 citation statements)

References 24 publications

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“…The structural pattern of this lesion has recently been well characterized by both light and electron microscopy (Inamura et al, 1987;Smith et al, 1988). Its occurrence could be detected already in the early period of recirculation, indicating that it precedes by many hours the onset of postischemic seizure activity.…”

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confidence: 94%

Decrease of Glutamate Decarboxylase Activity in Substantia Nigra and Caudoputamen following Transient Hyperglycemic Ischemia in the Rat

Folbergrová

Smith

Inamura

et al. 1989

J Cereb Blood Flow Metab

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Summary: Glutamate decarboxylase (GAD) activity was determined in caudoputamen (CP), substantia nigra (SN), and cerebral cortex (CCX) after 19-22 h of recirculation following 10 min of transient ischemia in hyperglycemic rats, i.e., under the conditions when previously a pro nounced nerve cell damage was demonstrated in both CP and SN. The present results demonstrate a decrease of GAD activity in SN by 30% and in CP by 22% and no change in CCX. No statistically significant change in GAD activity could be detected in SN, CP, or CCX 1,4, It is well established that preischemic hypergly cemia worsens the brain damage and the clinical outcome following ischemia, as compared to isch emia of corresponding duration and density under normoglycemic conditions (Myers and Yamaguchi, 1977;Siemkowicz and Hansen, 1978;Myers, 1979;Rehncrona et al., 1981; Pulsinelli et al., 1982a;Smith et al., 1988). In hyperglycemic rats even a short period of transient ischemia has been shown to lead to generalized seizures occurring within 18-26 h of recirculation, ending in the death of the an imal (Warner et al., 1987;Smith et al., 1988 897and 7 days following 10 min of ischemia in normoglyce mic animals. The decrease of GAD activity in SN at the time preceding the onset of postischemic seizures sug gests that there may be an imbalance between augmented excitatory and decreased inhibitory transmission in SN. We tentatively conclude that this may increase the prob ability of generalized seizures in the postischemic period following ischemia in hyperglycemic animals. Key Words: Caudoputamen-Cerebral ischemia-Glutamate decar boxylase-Hyperglycemia-Substantia nigra.mechanism underlying the development of this postischemic seizure activity is not known.Brain damage following transient ischemia in nor moglycemic animals is confined mostly to the so called selectively vulnerable regions comprising hippocampus, neocortex, caudoputamen (CP), and some other structures (e.g., Pulsinelli et al., 1982b;Smith et al. , 1984). In hyperglycemic rats, in addi tion, an extensive lesion has been demonstrated in the pars reticulata of the substantia nigra (SN) (Smith et al., 1987.The structural pattern of this lesion has recently been well characterized by both light and electron microscopy (Inamura et al., 1987;Smith et al., 1988). Its occurrence could be detected already in the early period of recirculation, indicating that it precedes by many hours the onset of postischemic seizure activity. The findings of these studies and the results concerning changes of energy metabo lites in SN under these conditions (Inamura et al., 1988) suggest that both excitotoxic damage and marked lactic acidosis may be responsible for the pathogenesis of this lesion. The SN has been identified as a critical brain site that plays a major role in the regulation of seizure propagation (Gale, 1985(Gale, , 1986. It has been sug gested that nigral efferents that are permissive or facilitative to seizure propagation are subject to in hibition by ",-aminobutyrate (GABA) and opiates...

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confidence: 94%

Decrease of Glutamate Decarboxylase Activity in Substantia Nigra and Caudoputamen following Transient Hyperglycemic Ischemia in the Rat

Folbergrová

Smith

Inamura

et al. 1989

J Cereb Blood Flow Metab

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“…- 21 In the present study, increasing intraischemic brain temperature converted ischemic cell injury to frank infarction in cortical, hippocampal, striatal, and thalamic areas. In contrast, shamoperated rats in which brain temperature was elevated to 39° C for 20 minutes to simulate ischemic brain temperatures showed no histopathological alterations.…”

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confidence: 99%

“…In this regard, damage to the substantia nigra pars reticulata occurs in rats made hyperglycemic prior to global forebrain ischemia. 21 Recently, the destruction by excitotoxins of striatal neurons has been reported to damage the ipsilateral substantia nigra pars reticulata-a remote consequence that could be prevented by y-aminobutyric acid (GABA) agonist. 24 In the present study, transient ischemia carried out at 39° C may increase the vulnerability of striatal GABAergic neurons, resulting in an imbalance between neuronal excitation and inhibition and subsequent necrosis of the pars reticulata.…”

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confidence: 99%

Effects of normothermic versus mild hyperthermic forebrain ischemia in rats.

Dietrich

Busto

et al. 1990

Stroke

311

100

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We compared the neuropathological consequences of global forebrain ischemia under normothermia versus mild hyperthermia. Twenty-one rats underwent 20 minutes of four-vessel occlusion during which brain temperature was maintained at either 37° C (normothermia, n=9) or 39° C (hyperthermia, n=12). Quantitative neuropathological assessment was conducted 1 or 3 days later. At 1 day following the ischemic insult, normothermic rats demonstrated neuronal injury mainly confined to the most dorsolateral striatum. By 3 days, ischemic cells were present throughout the striatum and CA1 hippocampus in normothermic animals. Compared with normothermic rats, intraischemic hyperthermia significantly increased the extent and severity of brain damage at 1 day after the ischemic insult. Areas of severe neuronal necrosis and frank infarction included the cerebral cortex, CA1 hippocampus, striatum, and thalamus. Morphologic damage was also detected in the cerebellum and pars reticulata of the substantia nigra. An overall mortality rate of 83% was demonstrated at 3 days in the hyperthermic ischemic group. We conclude that intraischemic hyperthermia 1) markedly augments ischemic brain damage and mortality compared with normothermia, 2) transforms ischemic cell injury into frank infarction, and 3) accelerates the morphological appearance of ischemic brain injury in regions usually demonstrating delayed neuronal necrosis. These observations on mild hyperthermia may have important implications for patients undergoing cardiac or cerebrovascular surgery as well as patients following cardiac arrest or those with stroke-in-evolution. (Stroke 1990;21:1318-1325)

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“…In addition no other brain area showed any side difference in damage that would suggest an alternative modulatory effect. Some evidence indicates that the lesion observed in SNPR following ischemia under hyperglycemic conditions is at least partly excitotoxic (Inamura et al 1987(Inamura et al , 1988 and caused by an imbalance between excitatory and inhibitory input. It is possible that a decrease in the inhibitory input, e.g.…”

Section: Discussionmentioning

confidence: 97%

“…They rather have the capability of antagonising the anticonvulsive effect of the GABA-ergic input. However, based upon the morphological damage following both seizures (Auer et al 1986;Ingvar et al 1987Ingvar et al , 1988 and ischemia under hyperglycemic conditions (Inamura et al 1987(Inamura et al , 1988 which includes swollen dendrites, EAAs in excess are though to be partly responsible for the neuronal damage and death in SNPR. One excitatory pathway to SNPR originates from the ipsilateral frontal cortex (Hassler et al 1982).…”

Section: Introductionmentioning

confidence: 98%

Frontal cortex lesion prior to hyperglycemic ischemia: no decrease in ensuing substantia nigra pars reticulata damage or fatal post-ischemic seizures

et al. 1992

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Preischemic hyperglycemia worsens brain damage after ischemia, and characteristically leads to post-ischemic seizures and a pan-necrotic lesion in substantia nigra pars reticulata (SNPR). The excitatory input to SNPR could contribute to the damage observed. By performing a unilateral frontal cortex lesion 6-19 days prior to the ischemia, we wanted to explore whether a decrease in excitatory input to the ipsilateral SNPR ameliorate the seizures or alter the light microscopical damage in SNPR. Our results demonstrate that unilateral frontal cortex lesion did not alter the development of fatal post-ischemic seizures after 10 min of ischemia in hyperglycemic subjects. Thus, 7/8 animals developed seizures and died within 20 h of recovery. This study also failed to show any difference between the left and right side in post-ischemic SNPR damage after 15 h of recovery in animals with preischemic unilateral frontal cortex lesion. Furthermore, no side difference was observed in any other brain region evaluated. The results thus suggest that the pan-necrotic lesion in SNPR after hyperglycemic ischemia is not caused by excessive excitatory input from frontal cortex. A decrease in the GABA-ergic inhibitory input from caudoputamen to SNPR may be a more important mechanism for the ensuing excitotoxic post-ischemic SNPR damage, and for seizure development.

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Substantia nigra damage induced by ischemia in hyperglycemic rats

Cited by 36 publications

References 24 publications

Decrease of Glutamate Decarboxylase Activity in Substantia Nigra and Caudoputamen following Transient Hyperglycemic Ischemia in the Rat

Decrease of Glutamate Decarboxylase Activity in Substantia Nigra and Caudoputamen following Transient Hyperglycemic Ischemia in the Rat

Effects of normothermic versus mild hyperthermic forebrain ischemia in rats.

Frontal cortex lesion prior to hyperglycemic ischemia: no decrease in ensuing substantia nigra pars reticulata damage or fatal post-ischemic seizures

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