Effect of topically applied serotonin on local cerebral blood flow.

Abstract

SUMMARY It has been hypothesized that acute lesions of the brain enlarge through an autodestructive process. Serotonin (5HT), a potent cerebral vasoconstrictor, is believed by some to mediate the process by reducing cerebral blood flow (CBF) in tissue surrounding the lesion. The hypothesis was tested in cynomolgus monkeys anesthetized with ketamine and nitrous oxide. Craniectomies, 7 mm in diameter, were performed in each parietal area. The dura was opened and polarographical electrodes of thin platinum wire were inserted into the parietal lobe cortex of each hemisphere. Mock cerebrospinal fluid (CSF) was irrigated continuously onto the brain surrounding the electrodes, from which local CBF was determined repeatedly by the hydrogen-clearance technique. After baseline CBF was established, solutions of 5HT in mock CSF (in concentrations of 5 X 10-' M, 5 X 10 5 M, and 5 X 10 s M) were irrigated onto one hemisphere while the opposite hemisphere served as control. SHT failed to change CBF.Although 5HT is a potent vasoconstrictor, under physiologic conditions it apparently is unable to effect hemodynamically significant constriction of the peripheral cerebral vasculature of the anesthetized monkey brain.IN RESPONSE to central nervous system injury, biogenic amines with vasoconstrictor properties are thought to be released from neurons and blood vessels in quantities sufficient to enlarge the original lesion. According to this hypothesis, an ischemic or traumatic lesion of the brain or spinal cord may enlarge because amines released by injury reduce blood flow sufficiently to infarct tissue surrounding the lesion.'" 8 Serotonin (5-hydroxytryptamine, 5HT) has been proposed as a mediator of this hypothetical selfpropagating zone of spreading ischemia 1 ' *• *• 8 because it is both a potent cerebral vasoconstrictor 914 and present in substantial concentrations in brain 15 and blood. 16 If the hypothesis is valid, local cerebral blood flow (CBF) should decrease when an appropriately concentrated solution of 5HT is applied topically to the brain. This paper reports the results of an investigation designed to test the hypothesis. Materials and MethodsYoung, adult cynomolgus monkeys (Macaca fascicularis) of both sexes weighing between 3 and 5 kg were initially given 50 mg of ketamine and 0.2 mg of atropine sulfate intramuscularly. They were then intubated with a cuffed endotracheal tube, placed on a volume respirator, and paralyzed with an intravenous injection of 0.3 mg of pancuronium. Anesthesia was maintained for the remainder of the experiment with an inhaled gas mixture of 70% N 2 O and 30% O 2 , supplemented with a continuous intravenous infusion of ketamine at 3 mg/kg/hr. Lactated Ringer's solution, to which was added 0.8 mg/100 ml of pancuronium, was infused continuously through a femoral vein cutdown at 16 ml/hr to maintain fluid and electrolyte balance and muscular paralysis. Rectal temperature was kept between 37° and 38°C with an externally applied heated pad. The animal was moderately hyperventilated at a respir...

Effect of Leukotrienes, 12-HETE, Histamine, Bradykinin, and 5-Hydroxytryptamine on in vivo Rabbit Cerebral Arteriolar Diameter

“…Our results support a va soconstrictor role for 5-HT, but the relatively weak response, even at higher concentrations, argues against an important role for 5-HT in vivo. The same opinion was expressed by Martins et al (1978) who showed that topical application of 5-HT on pial arterioles of monkeys had no effect. Interestingly, it has been shown in other species that perivascular application of 5-HT to pial vessels affects tone, de pending on the resting diameter of the vessel.…”

Subarachnoid hemorrhage—induced upregulation of the 5-HT1B receptor in cerebral arteries in rats

“…The relationship between 5-HT and cerebral vasospasm (following aneurysm rupture) has a very long, but not particularly distinguished, history and has been a warmly debated issue. 4,5,23 Indeed, the notion of the possible involvement of 5-HT in cerebral vasospasm is not new. During the 1970s and 1980s a number of publications appeared on the subject including papers on data from in vitro and in vivo studies on the contractile capacity of 5-HT in relation to In the MCA and BA there was approximately four times more mRNa coding for the 5-HT 1B receptor in cerebral arteries from rats with experimental SAH compared with controls.…”