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

Abstract

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...

Estradiol Alters Only GAD67 mRNA Levels in Ischemic Rat Brain with No Consequent Effects on GABA

“…Fraham et al (2004) observed no differences in the numbers of GAD mRNA-stained cells in the cortex and hippocampus at 7 and 30 days after focal ischemia. This is in contrast to studies that have showed both ischemiainduced increases and decreases in the cellular steady-state level of striatal and cortical GAD mRNA (Folbergrova et al , 1989; Francis and Pulsinelli, 1982; Fukatsu et al , 2002; Najlerahim et al , 1991; Saji et al , 1994; Salin and Chesselet, 1993). In different animal models of cerebral ischemia, GAD protein was observed to be altered after stroke for days (Kang et al , 2002) or even weeks (Salin and Chesselet, 1993; Yamada et al , 1994).…”

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

“…However, the damage after ischemia with normoglycemia appears later, after a longer "maturation period" as compared to ischemia with hyperglycemia. Folbergrovfi et al (1989) showed that 10 rain of ischemia under hyper-but not normoglycemic conditions decreased the glutamic acid decarboxylase content in SNPR at 24 hrs of recirculation, indicating a decrease at this time-point in the GABA-ergic input to SNPR following ischemia with hyperglycemia. We therefore suggest that an increased excitatory influence on SNPR favouring the development of late post-ischemic seizures and resulting in SNPR damage following ischemia in hyperglycemic subjects, is to some extent caused by decreased inhibition from caudoputamen.…”

Early intervention combining Chinese and Western medicine in traumatic brain injury with diffuse axonal injury: A report of three cases

“…These phenomena induce metabolic stress, energy failure, ionic imbalance, and ischemic injury. 24 , 25 In severe TBI, cerebral blood flow reduction also occurs due to brain swelling, causing secondary ischemia. Cells in an ischemic environment will die within minutes.…”