TRPV1 activation results in disruption of the blood–brain barrier in the rat

Abstract

1 We have examined the role of TRPV1 activation in disrupting the blood-brain barrier by measuring the permeability of single pial venular capillaries in anaesthetized rats. 2 Capsaicin application to the brain surface resulted in increased permeability, maximal 2.170.12 Â 10 À6 cm s À1 (mean7s.e.m.) with log EC 50 À4.570.10. Substance P methyl ester gave a similar response (maximal 2.070.07, n ¼ 6, log EC 50 À4.870.07), but the selective NK 2 agonist, b-Ala 8 -NKA 4-10 peptide, had no effect. Although CGRP decreased the permeability of venules (log EC 50 10.370.11), its receptor antagonist CGRP 8-37 had no effect on the response to capsaicin. 3 The TRPV1 antagonist capsazepine (1 mM) reduced the response to capsaicin (100 mM), from 1.7870.15 to 0.6370.10 (n ¼ 4). The NK 1 receptor antagonists GR205171 (100 mM) and SDZ NKT 376 (1 mM) also reduced the response to capsaicin (from 1.7570.14 to 0.4670.08; n ¼ 6, and from 1.8570.13 to 0.4870.05; n ¼ 5, respectively), indicating that capsaicin acts via TRPV1 in series with NK 1 . 4 Starch microspheres were used to produce transient focal ischaemia. Permeability was increased on reperfusion to a greater extent and more rapidly in vessels with diameter greater than 40 mm than those less than 15 mm. Capsazepine given intraperitoneally during ischaemia reduced the permeability increase in small venules from 5.970.3 to 2.470.1, and from 11.470.8 to 5.170.9 in large venules. 5 In conclusion, the TRPV1 receptor is active in the brain microvasculature and has its permeabilityincreasing effect via substance P. It also plays a role in the immediate blood-brain barrier disruption following ischaemia-reperfusion.

Roles of dorsal column pathway and transient receptor potential vanilloid type 1 in augmentation of cerebral blood flow by upper cervical spinal cord stimulation in rats

“…It also has been reported that TRPV1 is found in the brain on astrocytes and pericytes, which are closely associated with vasculature (Toth et al, 2005). TRPV1 receptor is active in the brain microvasculature and exerts its permeability-increasing effect via substance P (Hu et al, 2005). In the present study, local administration of RTX on C1-C2 spinal segments did not interrupt the augmentation of CBF or the reductions of CVR by cSCS.…”

TRPV1 Gates Tissue Access and Sustains Pathogenicity in Autoimmune Encephalitis

“…Broad expression patterns have fostered the view that central TRPV1 plays a role in pain processing and thermoregulation, and independent studies have suggested that PANEM cells may all express TRPV1, characterizing the BBB as a TRPV1-rich microenvironment (18,20,22). Activation of TRPV1 by application of the agonist capsaicin directly to the brain disrupts BBB integrity (23), and peripheral TRPV1 stimulation also opens the BBB and blood spinal cord barriers (BSCB) (24), supporting recent evidence that TRPV1 may modify cytokine signaling during CNS neuroinflammation and implying a disease-modifying role (25).…”

Transient Receptor Potential Vanilloid Subtype 1 Mediates Microglial Cell Death In Vivo and In Vitro via Ca2+-Mediated Mitochondrial Damage and CytochromecRelease

“…This results in excessive mitochondrial Ca 2ϩ loading and subsequent mitochondrial disruption, leading to neuronal cell death (17,18). Activation of TRPV1 by treatment with CAP was found to increase glutamate release from nigral slices (19), produce hypokinesia in parallel with decreased nigrostriatal neuron activity (20,21), and disrupt the blood-brain barrier following ischemia-reperfusion (22). Several lines of evidence have implicated 12-HPETE, an endogenous TRPV1 agonist (10), in the induction of long-term depression in the hippocampus (23) and neurodegeneration in mesencephalic cultures (24).…”