Perivascular Sensory Nerves Research Articles

The role of neuroeffector mechanisms in cerebral hyperperfusion syndromes

Cerebral hyperperfusion, a state in which blood flow exceeds the metabolic needs of brain, may complicate a number of neurological and neurosurgical conditions. It may account for the propensity with which hemorrhage, cerebral edema, or seizures follow embolic stroke, carotid endarterectomy, or the excision of large arteriovenous malformations, and for some of the morbidity that accompanies acute severe head injury, prolonged seizures, and acute severe hypertension. Hyperperfusion syndromes have in common acute increases in blood pressure, vasodilatation, breakdown of the blood-brain barrier, and the development of cerebral edema. These common features suggest the possibility that they share the same pathogenic mechanisms. It was believed until recently that reactive hyperemia was caused primarily by the generation of vasoactive metabolites, which induced vasodilatation through relaxation of vascular smooth muscle. However, the authors have recently established that the release of vasoactive neuropeptides from perivascular sensory nerves via axon reflex-like mechanisms has a significant bearing upon a number of hyperperfusion syndromes. In this article, the authors summarize their data and discuss possible therapeutic implications for blockade of these nerves or their constituent neuropeptides.

Release of Vasoactive Peptides from Autonomic and Sensory Nerves

Release of specific vasoactive peptides occurs upon activation of perivascular parasympathetic (vasoactive intestinal polypeptide and peptide histidine isoleucine), sympathetic (neuropeptide Y) and sensory (calcitonin gene-related peptide and tachykinins) nerves. These peptides may serve as cotransmitters with acetylcholine and noradrenaline with interactions both at the pre- and postjunctional levels. Some long-lasting nonadrenergic, noncholinergic vascular effects upon nerve activation may thus be peptide-mediated. Strong activation seems to be necessary for peptidergic transmission in the parasympathetic and sympathetic system while local sensory mechanisms may occur even at single impulses.

Capsaicin and blood-brain barrier permeability

The influence of perivascular sensory afferent nerve fibres upon the permeability of the blood-brain barrier was examined in halothane-anaesthetised rats. Blood-brain barrier permeability was assessed by the rate of transfer of the small neutral amino acid, [ 14C]α-aminoisobutyric acid, from blood to brain and by gross extravasation of Evans blue albumin. In every brain area examined, the acute administration of capsaicin (0.15–5 μmol/kg, i.v.) failed to alter significantly the passage into the brain of the small neutral amino acid tracer or to effect dye extravasation. Capsaicin, at concentrations which cause the release of vasoactive neuropeptides from nerve endings and increase vascular permeability in peripheral tissues, does not increase the permeability of the blood-brain barrier.