Metabolism of monoamine neurotransmitters in the evolution of infarction in ischemic striatum

The cerebral dialysis technique was employed to monitor extracellular concentrations of dopamine (DA), norepinephrine (NE), dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the dorsal hippocampus of gerbils before and after cerebral ischemia induced by carotid artery occlusion. Extracellular concentrations of DA and NE in the dorsal hippocampus increased from baseline levels of less than 35 fmol/collection interval to 180 and 200 fmol/collection, respectively, within 36 minutes following carotid artery ligation (n = 8 animals). Extracellular concentrations of the DA metabolites, DOPAC and HVA, did not change significantly following carotid artery ligation. These data demonstrate that ischemia in the dorsal hippocampus is associated with a mared release of DA and NE. This release may contribute to the selective vulnerability of the dorsal hippocampus to neuronal damage during ischemia.

Section: Discussionmentioning

confidence: 95%

Ischemia in the dorsal hippocampus is associated with acute extracellular release of dopamine and norepinephrine

Bhardwaj

Brannan

Martinez-Tica

et al. 1990

“…Additional evidence of continued metabolism is the fact that dopamine nerve terminals isolated from the ischemic cerebrum can actively take up dopamine in vitro for up to 8 hours after ischemia (Weinberger and Nieves-Rosa, 1987). Tissue levels of the dopamine metabolites, DOPAC and HVA are also elevated for up to 7 hours after ischemia -additional evidence that dopamine metabolism continues during tissue ischemia (Weinberger and Nieves-Rosa, 1987).…”

Section: Discussionmentioning

confidence: 97%

Pentobarbital inhibits extracellular release of dopamine in the ischemic striatum

Bhardwaj

Brannan

Weinberger

1990

We examined whether pentobarbital (PB) inhibited the acute extracellular release of dopamine that occurs in the striatum following the onset of ischemic injury in the gerbil model of stroke. The cerebral dialysis technique was employed to monitor striatal extracellular dopamine concentrations before and after carotid artery occlusion while perfusing either a control solution of artificial cerebrospinal fluid (CSF) or a 1 mM solution of pentobarbital in CSF (PB/CSF). During perfusion with CSF, extracellular dopamine increased from a baseline concentration of 0.40 +/- 0.09 (SEM) pmoles/10 minute collection interval to 30.0 +/- 9.0 pmoles/10 minutes after carotid artery occlusion. In contrast, during perfusion with PB/CSF, dopamine levels increased from a baseline of 1.37 +/- 0.3 pmoles/10 minutes to 8.30 +/- 2.6 pmoles/10 minutes; this increase was significantly less than the increase in controls. In animals with established ischemia, repeatedly alternating the perfusion fluid between CSF and PB/CSF demonstrated that dopamine concentrations were significantly increased with CSF alone and decreased with PB/CSF. These findings demonstrate that pentobarbital perfusion either before or following the onset of ischemia inhibits extracellular release of dopamine in the striatum. Inhibition of neurotransmitter release may, in part, be responsible for the protective effect of pentobarbital in ischemic brain injury.

“…C A D F in the ischemic striatum is not seen uniformly throughout the neuropil and varies from region to region in time. This accounts for the continued presence of C A D F even though levels of CA fall precipitously to 25% to 30% of control in both the ischemic cerebral hemisphere (Lavyne et al, 1975;Lust et al, 1975;Mrsulja et al, 1976;Zervas et al, 1974) and striatum (Zervas et al, 1974;Weinberger and Nieves-Rosa, 1987) within two hous after stroke, probably secondary to acute release of CA from nerve terminals (Lavyne et al, 1975;Meyer et al, 1974;Brannan et al, 1987). Studies of striatal D A release in vivo with electrochemical detection have shown that there is acute massive release of DA, corresponding to depletion of visible CADF in the striatum 2 hours after stroke (Ahagon et al, 1980).…”

Section: Discussionmentioning

confidence: 95%

Monoamine neurotransmitters in the evolution of infarction in ischemic striatum: morphologic correlation

Weinberger

Nieves-Rosa

1988

Self Cite

Evolution of infarction following cerebral ischemia is a delayed process, with spongiform degeneration of the neuropil occurring 6 to 8 hours after onset of ischemia. The brains of gerbils with stroke following unilateral carotid artery ligation were examined for catecholamine-derived fluorescence (CADF) by the Falck-Hillarp technique to study the relationship of catecholamine (CA) metabolism with damage to the neuropil. CADF could still be identified in the striatum for up to 16 hours after stroke and there appeared to be spongiform degeneration of the neuropil in relation to accumulations of CADF at 7 and 16 hours after stroke. Pretreatment of gerbils with a-methyl-p-tyrosine 400 mg/kg 6 hours prior to carotid ligation depleted the striatum of CADF until 16 hours after stroke and appeared to reduce the spongiform degeneration of the neuropil, though it did not affect ischemic degeneration of neuronal cell bodies. The continued presence of CADF in the striatum for up to 16 hours after stroke supports the previously reported findings that CA nerve terminals are still functional for 8 hours after stroke and that CA metabolism continues even though levels of CA are reduced immediately after onset of ischemia due to carotid artery ligation.