Cortical injury without ischemia produced by topical monoamines.

Abstract

SUMMARY Responses to monoamines perfused over the cortical surface through modified pial windows were monitored in 106 cats. Norepinephrine (NE) and serotonin (5-HT) were diluted in mock CSF to concentrations of 50 and 500 ng/ml respectively, levels at or near the maximum concentrations to which the cortical surface might be exposed in subarachnoid hemorrhage or damage to nearby neurons. Each cat had simultaneous one-hour perfusions of monoamine solution over one hemisphere and a control solution over the other hemisphere thus serving as its own control.The perfusion solutions were observed to be restricted to the area of the pial window, and minimal histological damage was seen with the perfusion technique. The 5-HT perfusions were associated with an almost 20% narrowing of small pial arteries and arterioles but no significant effect on regional cerebral blood flow (rCBF), cortical water content or cortical function as monitored by EEG and somatosensory evoked potentials (SEP). In contrast, NE caused cortical edema and changes in the EEG and SEP's without significant vascular effect. These results suggest a non-ischemic toxicity of NE released by subarachnoid hemorrhage or cerebral damage.Stroke, Vol 13, No 1,1982 THERE has been considerable interest in recent years in the roles of two monoamines, norepinephrine (NE) and serotonin (5-hydroxytryptamine, 5-HT), in normal and pathological cerebral events. Both are present in the brain at concentrations adequate for physiological function and are widely considered to act as neurotransmitters. 15 Fluorescent histochemical techniques have demonstrated NE and 5-HT in axon terminals of the cerebral cortex, to which they project from brainstem neurons. 610Some investigators have assigned a physiological role in cerebral blood flow (CBF) control to NE 11,12 and 5-HT, 13 and this concept has been supported by observed effects of both agents on pial vessel diameter. 1417 It has been suggested that these monoamines, released by subarachnoid hemorrhage, are responsible for arterial spasm, diminished CBF, and impaired neurological function. 1820 Disturbances in concentration and metabolism of these monoamines in the cerebral cortex and in the cerebrospinal fluid (CSF) have been found not only in subarachnoid hemorrhage 21 " 23 but also in cerebral anoxia 2427 and in head trauma.28 " 31 It has been suggested that the release or redistribution of cortical NE and 5-HT are involved in the enlargement of ischemic and traumatic lesions.22,32 " S4Attempts to study the effects of exogenous monoamines on the brain have been hampered by cerebral inaccessibility. Given parenterally, NE and 5-HT cross the blood-brain barrier (BBB) poorly or not at all. 35" 41 The value of monoamine injections and infusions into the ventricles and subarachnoid cisterns is limited by their rapid clearance with CSF flow 4244 and by the inability to control their distribution or to identify their sites of action. 48 51 may be complicated by blood pressure changes or the presence of other subst...

Biphasic striatal dopamine release during transient ischemia and reperfusion in gerbils.

“…This conclusion was supported by the observations of Stein and Cracco 10 that the topical application of catecholamines to cortical tissue has toxic effects even in the absence of ischemia. These investigations led Clemens and Phebus 8 and Globus et al 11 to propose that extracellular accumulation of dopamine, or its metabolites, may have a mechanistic role in the pathogenesis of ischemic striatal neuronal injury.…”

Nerve terminal damage in cerebral ischemia: protective effect of alpha-methyl-para-tyrosine.

“…Furthermore, there is some evidence that extraneuronal catecholamines may be toxic to neuronal structures: When norepinephrine is injected into the capillaries of a pial window, regional necrosis of cerebral tissue occurs. 16 Necrosis does not occur when 5-HT is injected, even with an equivalent amount of regional ischemia. 16 Acute release of endogenous catecholamine does not explain the delayed damage to nerve terminals that occurs after eight hours of ischemia, though it may be involved in the initial damaging process.…”

Effects of the Noradrenergic System in Rat White Matter Exposed to Oxygen–Glucose DeprivationIn Vitro

“…This high extracellular NE concentration is intensely neurotoxic (Stein and Cracco, 1982;Globus et al, 1989) and may play a key role in ischemic neuronal damage . The mechanism of this release under ischemic conditions involves Na ϩ -dependent reversal of the monoamine uptake carrier (Vizi, 2000;Sumiya et al, 2001).…”