Cerebral circulatory and metabolic effects of perivascular neurotransmitters

In this article we review the most recent literature that concerns the various neurotransmitters that are known to innervate the cerebral circulation. The best characterized of these systems (the adrenergic and serotonergic pathways) are discussed extensively, but other putative neurovascular pathways (cholinergic and peptidergic nerves) was covered. The review will be divided into five major sections: the origin and nature of the perivascular nerve fibers in the cerebrovascular bed (this section encompasses both morphological and biochemical investigations); the response of isolated cerebral vessels to neurotransmitters and transmural nerve stimulation (covering the uptake and release of transmitters by brain vessels as well as the pre- and postsynaptic effects of these agents on cerebrovascular smooth muscle); the effects of neurotransmitter and other vasoactive agents on cerebral perfusion and metabolism in vivo. This section includes the effects of perivascular nerve stimulation or ablation on cerebral blood flow as well as on capillary (i.e., blood-brain barrier) properties. The regional metabolic effects of neurotransmitters are compared to their known effects on neuronal function; the involvement of various neurotransmitters in a number of cerebrovascular diseases (in particular, migraine, cerebral vasospasm following subarachnoid hemorrhage and cerebral ischemia, or stroke); and we attempt to synthesize the ever-increasing literature on the origin and function of the multiple innervation of two other noncerebral, intracranial tissues: the choroid plexus and the dura mater.