Associations between neuropeptide Y nerve terminals and intraparenchymal microvessels in rat and human cerebral cortex

Abstract

Neuropeptide Y (NPY) can influence local brain perfusion, possibly via direct relationships with the microvascular bed. To evaluate this possibility, the authors quantitatively analyzed by light and electron microscopy the morphological associations between immunostained NPY neuronal elements and intraparenchymal microvessels in the rat and human cerebral cortex. At the light microscopic level in the rat frontoparietal cortex, about 16% of NPY neurons and large proximal processes as well as a subset of nerve terminals not affected by double sympathectomy were associated with penetrating arterioles and local microvessels. In human temporal cortex, a dense network of NPY nerve fibers was observed, many of which approached and/or contacted intracortical vessels. At the ultrastructural level, 14% of NPY axonal varicosities in the rat cerebral cortex were considered perivascular and associated with capillaries (approximately 70%) or microarterioles (approximately 30%). They were particularly enriched in the immediate vicinity (< 0.25 micron) of the microvessels, where the perivascular astrocytic leaflets represented a frequent target. In human cerebral cortex, NPY varicosities were observed in proximity to microvessels corresponding primarily to capillaries. Perivascular NPY varicosities never established synaptic junctions with vascular or astroglial elements. The results show that central NPY nerve terminals associate with microvessels and perivascular astroglial cells in the rat and human cerebral cortex. Thus, NPY released from these nerves could possibly influence (via a parasynaptic mode of action) vascular and/or astrocytic functions depending on the distribution of NPY receptors in these cellular compartments. These results provide morphological support for the effects of NPY on brain perfusion and homeostasis.

Cortical GABA Interneurons in Neurovascular Coupling: Relays for Subcortical Vasoactive Pathways

“…This was particularly striking for NOS neurons emphasizing not only their perivascular localization (Estrada and DeFelipe, 1998) but their permissive role in functional hyperemia (Lindauer et al, 1999;Iadecola, 2004). This finding also agrees with previous reports of intimate associations between VIP, NPY, or NOS axonal varicosities or dendrites and cortical microvessels (Eckenstein and Baughman, 1984;Iadecola et al, 1993;Chédotal et al, 1994b;Abounader and Hamel, 1997).…”

“…2 D). This highlights the opposite roles of NO and NPY, respectively, potent dilator and constrictor, and the interpretation of their extensive colocalization (Kubota et al, 1994) as a mean to spatially limit the vasodilatory effect of the highly diffusible gas NO (Abounader and Hamel, 1997;Estrada and DeFelipe, 1998). In contrast to dilatations, constrictions were reversible.…”

Hypocretin1/orexinA-immunoreactive axons form few synaptic contacts on rat ventral tegmental area neurons that project to the medial prefrontal cortex

“…Hcrt/Ox have also shown vasomotor effects through its activation of nitrergic or GABAergic neurotransmission in the solitary tract [53]. Neuropeptide Y, a well-known peptide involved in microvascular functions [54], is contained in hypothalamic neurons targeted by Hcrt/Ox axons [55]. Altogether, this suggests that the Hcrt/Ox system could be involved in vascular tone regulation also in the VTA.…”

High Plasma Levels of Neuropeptide Y Correlate With Good Clinical Outcome But are not Correlated to Cerebral Blood Flow or Vasospasm After Subarachnoid Hemorrhage

“…It is considered the most potent endogenous vasoconstrictor even surpassing the potency of noradrenaline 6,7 and has been shown to be costored in the sympathetic perivascular nerve fibers of the cerebral arteries along with noradrenaline. [8][9][10] Because of NPY's potent vasoconstrictor properties, it has been suggested to be a regulator of cerebral blood flow (CBF) as well as a factor in cerebral vasospasm and DCI. 9 During the 1990s, several animal studies [11][12][13][14][15][16] and clinical studies [17][18][19][20][21] investigated the possible relationship between SAH, DCI, vasospasm, and NPY.…”