Chronic parasympathetic sectioning decreases regional cerebral blood flow during hemorrhagic hypotension and increases infarct size after middle cerebral artery occlusion in spontaneously hypertensive rats.
Regional cerebral blood flow (rCBF) during controlled hemorrhagic hypotension (140-20 mm Hg) was assessed 10-14 days after chronic unilateral sectioning of parasympathetic and/or sensory fibers innervating pial vessels in spontaneously hypertensive rats (SHR). rCBF was measured in the cortical barrel fields bilaterally by laser Doppler blood flowmetry. Immunohistochemistry of middle cerebral artery (MCA) whole mount preparations was used to verify the surgical lesion. During hemorrhagic hypotension, rCBF was equivalent on the two sides in shams, after selective sensory denervation, or in parasympathetically sectioned animals exhibiting small decreases (less than or equal to 30%) in immunoreactive vasoactive intestinal peptide (VIP)-containing fibers. After chronic parasympathetic denervation, decreases in perfusion pressure were accompanied by greater reductions in rCBF on the lesioned side; changes in vascular resistance were also attenuated on that side. The rCBF response to hypercapnia (PaCO2 50 mm Hg), however, was symmetrical and robust. To examine the effects of impaired neurogenic vasodilation on the pathophysiology of cerebral ischemia, infarct size was measured 24 h following tandem MCA occlusion in denervated animals. Infarction volume was larger after selective parasympathetic sectioning (sham, 156 +/- 27 vs. 196 +/- 32 mm3, respectively) but only in those denervated animals demonstrating greater than or equal to 40% decrease in immunoreactive VIP-containing fibers within the ipsilateral MCA. Lower than expected blood flow/perfusion pressure in the cortex distal to an occluded blood vessel may relate the observed blood flow responses to the occurrence of larger cortical infarcts in parasympathetically denervated animals. If true, the findings suggest a novel role for neurogenic vasodilation in the pathophysiology of cerebral ischemia and in rCBF regulation within the periinfarction zone.
Koketsu
N
N
Stroke Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Moskowitz
M A
MA
Kontos
H A
HA
Yokota
M
M
Shimizu
T
T
D000818:Animals; D001794:Blood Pressure; D001921:Brain / Q000098:blood supply*; D001923:Brain Chemistry; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology; D002536:Cerebral Arteries / Q000503:physiopathology; D002543:Cerebral Hemorrhage / Q000503:physiopathology*; D002544:Cerebral Infarction / Q000473:pathology* / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D006935:Hypercapnia / Q000503:physiopathology; D007022:Hypotension / Q000503:physiopathology*; D007150:Immunohistochemistry; D008297:Male; D010275:Parasympathetic Nervous System / Q000503:physiopathology*; D051381:Rats; D011918:Rats, Inbred SHR; D014660:Vasoactive Intestinal Peptide / Q000032:analysis
D014660:Vasoactive Intestinal Peptide