A procedure for occluding the stem of the proximal middle cerebral artery of the rat is described. The operation is performed under anaesthesia through a small subtemporal craniectomy. After occlusion, 3 animals were perfused with carbon block and 8 with a FAM fixative (40% formaldehyde, glacial acetic acid, and methanol). The findings were compared with sham-operated animals. Carbon black studies demonstrated an area of impaired perfusion corresponding to the territory of the occluded artery in each animal. Neuropathological studies invariably showed that there was ischaemic brain damage in the cortex and basal ganglia. The frontal cortex was involved in every animal, as was the lateral part of the neostriatum; the sensorimotor and auditory cortex were involved in most animals, whereas the occipital cortex and medial striatum were involved only infrequently. The damage produced by ischaemia could be readily distinguished from the small local lesion seen at the surgical site in sham-operated animals. The ability to produce a consistent focal ischaemic lesion in the rodent brain provides a technical approach that is sufficiently reproducible to enable investigation of the pathophysiology of ischaemia using recently developed autoradiographic and neurochemical methods.

Studies of patients and animals with brain lesions have implicated the hippocampal formation in spatial, declarative/relational and episodic types of memory. These and other types of memory consist of a series of interdependent but potentially dissociable memory processes-encoding, storage, consolidation and retrieval. To identify whether hippocampal activity contributes to these processes independently, we used a novel method of inactivating synaptic transmission using a water-soluble antagonist of AMPA/kainate glutamate receptors. Once calibrated using electrophysiological and two-deoxyglucose techniques in vivo, drug or vehicle was infused chronically or acutely into the dorsal hippocampus of rats at appropriate times during or after training in a water maze. Our findings indicate that hippocampal neural activity is necessary for both encoding and retrieval of spatial memory and for either trace consolidation or long-term storage.

Distribution studies disclosed that all major cerebral arteries and cortical arterioles of the cat were invested with fme varicose nerve fibers that contained calcitonin generelated peptide (CGRP)-like immunoreactivity; the trigeminal ganglia likewise contained CGRP immunoreactivity. Sequential immunostaining with antibodies to CGRP and to substance P (SP) revealed identical distributions of these two peptides in trigeminal ganglia and cerebrovascular nerve fibers, suggesting that CGRP and SP are colocalized in these nerves. CGRP completely disappeared from ipsilateral blood vessels after unilateral section of the trigeminal nerve. Exogenous CGRP was a potent relaxant of feline middle cerebral arteries in vitro (maximum relaxation, 10.5 ± 1.5 mN; concentration eliciting half-maximal response, 9.6 ± 1.3 nM). Perivascular microapplication of CGRP to individual cortical arterioles of chloralose-anesthetized cats provoked dose-dependent dilatations (maximum increase in diameter, 38 ± 5%; concentration eliciting half-maximal response, '-3 nM). CGRP was signifiw cantly more potent than SP as a cerebrovascular dilator, both in vitro and in situ. Chronic division of the ipsilateral trigeminal nerve in cats did not modify the magnitude of arteriolar responses to perivascular microapplication of either vasoconstrictor or vasodilator agents, but the duration of vasoconstrictor responses to norepinephrine (0.1 mM) or alkaline solutions (pH 7.6) was significantly increased. The cerebrovascular trigeminal neuronal system, in which CGRP is the most potent vasoactive constituent, may participate in a reflex or local response to excessive cerebral vasoconstriction that restores normal vascular diameter.Local cerebral blood flow is normally adjusted to meet local demands for energy generation that is almost exclusively met by the oxidative catabolism of glucose. The vasoactive products of cellular metabolism, with perivascular hydrogen ions, potassium ions, and adenosine being the most favored candidates, have long been considered primarily responsible for this dynamic regulation of cerebral blood flow (1). Cerebral blood vessels are, however, invested by nerve fibers that contain diverse neurotransmitters [norepinephrine, acetylcholine, 5-hydroxytryptamine, vasoactive intestinal polypeptide, peptide histidine isoleucine, neuropeptide Y, substance P (SP) and such]. Although these agents have direct vasomotor effects upon cerebral blood vessels, the explicit function of any of these perivascular neuronal systems in cerebrovascular regulation remains obscure (2, 3).The neuropeptide, calcitonin gene-related peptide (CGRP), has recently been identified from structural analysis of the products of calcitonin gene expression. Alternative processing of RNA transcribed from the calcitonin gene leads to the production, in neuronal tissue, of a 37-amino acid peptide, CGRP (4,5). CGRP-like immunoreactivity is present in many regions of the central nervous system (most notably the spinal cord, medullary and pontine nuclei, amygdala, a...

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