Experimental cerebral ischemia in Mongolian gerbils

Abstract

Light microscopic observations were carried out on Mongolian gerbils (Meriones unguiculatus) subjected to a partial cerebral ischemia by occlusion of the left common carotid artery at the neck. About 30% of gerbils developed an ischemic injury in the ipsilateral hemisphere and their brains revealed the following histopathologic features: 1. the changes were related to the intensity (duration) of the ischemic insult and to the time elapsed following release of the occlusion. The ischemic lesions appear to progress after re-establishment of the circulation and this presents one facet of a "maturation" phenomenon which seems to be a general principle applicable to various parameters of ischemic injury. The rate of "maturation" of the lesions is related to the intensity of the ischemic insult, a lesser intensity resulting in longer development of lesions. 2. The changes were either focal or diffuse in character. The former were assumed to be directly related to a vascular involvement; among the latter the topistic distribution of the hippocampal changes suggested a feature of selective vulnerability. 3. An indirect indication of neuronal recovery was surmised from observations on animals sacrificed after different periods following occlusions of the same duration. Also capable of recovery was a "reactive change" observed in the H3 neurons of the hippocampus. This change was characterized by central chromatolysis and resembled the "rimäre Reizung" of Nissl.

Quantitative autoradiography of [3H]‐MK‐801 binding sites in mammalian brain

“…Indeed, detailed pharmacological characterization of [3H]-MK-801 and [3H]-TCP binding sites in cortical membranes suggested an identical specificity (Wong et al, 1987 (Loo et al, 1986;Fagg, 1987;Foster & Wong, 1987 (Gundlach et al, 1986b;Largent et al, 1986). The lack of correspondence in regional distribution (Gundlach et al, 1985), together with the dramatic difference in pharmacological specificity between the sites labelled by [3H]-MK-801 and the a ligand (+)-[3H]-SKF 10,047 (Wong et al, 1987) ceptible to ischaemic insult appears to be the hippocampus, in particular the CAI region (Ito et al, 1975). This was readily detected in the present study by histological staining.…”

“…The gerbil provides a useful model for studying neuronal damage resulting from ischaemic insult since it lacks a Circle of Willis (Kahn, 1972). Thus unilateral occlusion of the carotid arterial blood supply produces ischaemic damage which is restricted to the occluded side (Harrison et al, 1973;Ito et al, 1975). The brain region which is most sus- (Gundlach et al, 1986b (Monaghan et al, 1984).…”

K+ channel openers prevent global ischemia-induced expression of c-fos, c-jun, heat shock protein, and amyloid beta-protein precursor genes and neuronal death in rat hippocampus.

“…These doses of KCOs are similar to those previously shown to prevent seizures (31). Glipizide (1 ttmol/5 ul; Pfizer Diagnostics) was injected intracerebroventricularly 20 min prior to openers. Control experiments were performed with intracerebroventricular injection of 0.9% NaCl under conditions used for openers.…”

“…Global forebrain ischemia leads to a complete neuronal death in the CAl field of the hippocampus after 7 days of recovery, whereas the adjacent CA3 sector and the dentate gyrus are largely more resistant (1,2). The main factors involved in the damage of neuronal tissue following ischemia are ATP depletion (3), intracellular acidosis (4), enhanced release and/or diminished reuptake of the excitatory transmitters glutamate and aspartate (5), generation of free radicals (6), and increased Ca2+ influx and K+ efflux (7,8).…”

Cerebral blood flow and edema following carotid occlusion in the gerbil.

“…18 Electrodes of 1 mm were made from Teflon-coated 90% platinum, 10% iridium wire, 100 n in diameter and the distal 0.5 mm tip of the electrode was bared. The electrodes were polarized 400 mv positive to a silver/silver chloride reference electrode placed subcutaneously in the back of the animal.…”