Masatsugu Nakai

Electrical stimulation of cerebellar fastigial nucleus increases cerebral cortical blood flow without change in local metabolism: Evidence for an intrinsic system in brain for primary vasodilation

We sought to determine whether the increase in regional cerebral blood flow (rCBF) elicited by electrical stimulation of the fastigial nucleus of the cerebellum (FN) is secondary to, or independent of, increased local cerebral metabolism (rGMR) in anesthetized (chloralose) paralyzed rats. rCBF and rGMR were determined autoradiographically in separate groups of animals with comparable blood gases and systemic pressure, by the [14C]iodoantipyrine and [14C]2-deoxyglucose methods respectively. In sham-operated controls, rCBF (n = 5) and rGMR (n = 5) were closely related in the 28 brain areas studied (r = 0.733; P less than 0.005). During FN stimulation, rCBF (n = 6) increased significantly in 24 of the 28 areas, the greatest increase being in the cerebral cortex (up to 215%). rGMR (n = 9) increased in only 15 areas, so that the correlation between rCBF and rGMR throughout the brain became weaker (r = 0.568; P less than 0.005). Where the rCBF increases were the greatest (particularly in the cerebral cortex), rGMR was unchanged. This suggests that the rCBF increase was not a consequence of the increased rGMR. We conclude that neurons originating in or passing through FN may influence local cerebral circulation through a primary cerebral vasodilatation not coupled to metabolism.

Parasympathetic cerebrovasodilator center of the facial nerve.

Functional studies have yet to be undertaken to establish which brain region subserves the parasympathetic regulation of the cerebral circulation. Using 31 anesthetized rats with precluded cervical sympathetic trunks, we therefore attempted to perform chemical stimulation of the greater petrosal nerve (GPN) cell group, which is a subgroup of the superior salivatory nucleus and sends off axons largely to the parasympathetic pterygopalatine ganglion via the GPN component of the facial nerve. The cerebrocortical blood flow was monitored with a laser-Doppler flowmeter. Unilateral stimulation of the GPN cell group by microinjection of L-glutamate reduced the ipsilateral cerebrocortical vascular resistance, maximally by 16.4 +/- 4.1% (mean +/- SD, n = 61). The response was not mediated by the classic muscarinic receptors of the cerebral vessel wall. However, pharmacological blockade of the peripheral parasympathetic ganglia and acute and chronic bilateral removal of the parasympathetic postganglionic fibers originating in the pterygopalatine ganglion abolished the response. The present data thus provide functional evidence that the GPN cell group may constitute a parasympathetic cerebrovasodilator center.

Global increase in cerebral metabolism and blood flow produced by focal electrical stimulation of dorsal medullary reticular formation in rat

We sought to determine whether the increases in local cerebral blood flow (LCBF) elicited by focal electrical stimulation within the dorsal medullary reticular formation (DMRF), are secondary to or independent of, increased local cerebral glucose utilization (LCGU). Rats were anesthetized (chloralose), paralyzed, artificially ventilated and arterial pressure and blood gases controlled. LCBF and LCGU were determined in two separate groups of animals, using the autoradiographic [14C]iodoantipyrine and [14C]2-deoxyglucose methods, respectively. In unstimulated controls, LCBF (n = 5) and LCGU (n = 5) were linearly related (r = 0.780; P less than 0.001) in the 27 brain regions studied. During DMRF stimulation LCGU increased significantly in 21 of the 27 regions, including cerebral cortex (up to 168% of control), thalamic nuclei (up to 161%) and selected ponto-medullary regions (e.g. parabrachial complex: 212%; vestibular complex: 147%). Along with LCGU, LCBF rose significantly in 25 regions (sensory motor cortex: 163%; anterior thalamus: 161%; parabrachial complex: 186%). Correlation analysis demonstrated that, during DMRF stimulation, the close relationship between LCBF and LCGU is preserved (r = 0.845; P less than 0.001) and that, in addition, the increase in LCBF (delta LCBF) is proportional to the increase in LCGU (delta LCGU) (delta LCBF = 2.18 delta LCGU + 6.92; r = 0.7729; P less than 0.001). Excitation of neurons or fibers within DMRF increases brain metabolism globally and blood flow secondarily. The DMRF appears to modulate cerebral metabolism globally, by as yet undefined pathways.

Effects of Aging and Chronic Hypertension on Cerebral Blood Flow and Cerebrovascular CO2 Reactivity in the Rat

We measured regional cerebral blood flow (rCBF) in young and old Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats by a minimally invasive microsphere technique. Blood flows to the cerebrum, diencephalon, mesencephalon, cerebellum and pons-medulla during normocapnia were determined. To test the ability of the vessels to dilate, rCBF was also measured during hypercapnia. Reactivity to CO2 was calculated as delta rCBF/delta paCO2. In the old SHR, blood flow to the pons-medulla (88 +/- 8 ml/min/100 g, mean +/- SEM) was markedly lower than that in the young SHR (107 +/- 4 ml/min/100 g, p < 0.05), whereas the difference of those values in the old and young WKY rats was slight (0.05 < p < 0.1). There were no differences in the values of blood flow to the cerebrum, diencephalon, mesencephalon or cerebellum between the young and old rats in both species. Cerebrovascular CO2 reactivity was markedly impaired in the old SHR (p < 0.05) compared to that in the young SHR, but the difference in reactivity in the WKY rats was not significant. The results indicate that blood flow to the pons-medulla is reduced in association with age, particularly in the hypertensive animals, and that the ability of the cerebral vessels to dilate is impaired homogeneously by the combination of chronic hypertension and aging.

Global cerebral vasodilatation elicited by focal electrical stimulation within the dorsal medullary reticular formation in anesthetized rat

We examined the effects of electrical stimulation of a restricted area of the dorsal medullary reticular formation (DMRF) on regional cerebral blood flow (CBF) in anesthetized (by chloralose), paralyzed (by curare) rats. CBF was measured in tissue samples by the Kety principle, with 14C-iodoantipyrine as indicator. Stimulation of DMRF elicited a widespread, significant increase in CBF in 12 of 13 areas. The increase in flow was greatest in cerebral cortex, up to 240% of control. However, it was also substantially increased in selected regions of telencephalon, diencephalon, mesencephalon, and lower brainstem, but not cerebellum. In contrast, electrical stimulation of the midline (interstitial nucleus of the medial longitudinal fasciculus) 1 mm medial to the DMRF did not change CBF. The increase in CBF evoked by DMRF stimulation persisted after transection of the spinal cord at C1 or cervical sympathetic trunk. We conclude that excitation of neurons originating in or passing through the DMRF can elicit a potent and virtually global increase of CBF. The effect appears to be mediated by intrinsic pathways of the central nervous system.

A minimally invasive technique for multiple measurement of regional blood flow of the rat brain using radiolabeled microspheres

To observe the rat brain blood flow with microspheres, a left ventricular catheter for sphere introduction was threaded into position via the right brachial artery. Cross-circulation with a donor rat was employed to prevent any mismatch between the infused and sampled blood volumes. Multiple measurements yielded stable flow data, and the responsiveness to hypercapnia was well preserved, irrespective of the dose of injected spheres (48 x 10(3) and 130 x 10(3)).

Chemical stimulation of the nucleus tractus solitarii decreases cerebral blood flow in anesthetized rats.

In anesthetized (chloralose and urethane), paralyzed and artificially ventilated rats, the neurons in the nucleus tractus solitarius (NTS) were chemically stimulated by microinjections of L-glutamate and the cerebral blood flow (CBF) was determined using a combination of labeled microspheres (either 57Co, 113Sn and 46Sc or 141Ce, 85Sr and 46Sc). Unilateral chemical stimulation of the NTS (n = 14) decreased CBF significantly in most brain areas. The decrease in CBF was not due to the decrease in arterial blood pressure (ABP) because the CBF of the whole cerebral cortex during the chemical stimulation of the NTS was significantly smaller (P less than 0.05) than the CBF during controlled hemorrhagic hypotension (n = 10). In another group of rats (n = 6), moderate hypertension was induced by blood transfusion. Unilateral chemical stimulation of the NTS in these rats decreased ABP but it remained within normotensive range. A significant (P less than 0.05) decrease in CBF (from 62 +/- 28 (mean +/- S.D.) to 48 +/- 23 ml.min-1.(100 g)-1) and increase in cerebrovascular resistance (from 1.9 +/- 1.2 to 2.6 +/- 1.2 mm Hg per [ml.min-1.(100 g)-1]) was observed in the whole cerebral cortex of these rats. Chemical stimulation of the NTS did not affect the reactivity of the cerebral vessels to hypercapnea (n = 5). These results suggest that the cell bodies within the NTS may play a role in the control of cerebral circulation.

Chemical stimulation of the rostral ventrolateral medullary pressor area decreases cerebral blood flow in anesthetized rats

In urethane-anesthetized, paralyzed and artificially ventilated rats, the neurons in the rostral ventrolateral medullary pressor area (VLPA) were chemically stimulated by microinjections of L-glutamate (1.7-5.0 nmole in 100 nl of 0.9% sodium chloride solution) and the cerebral blood flow (CBF) was determined using a combination of labeled microspheres (57Co, 113Sn and 46Sc). In one group of rats (n = 11), unilateral chemical stimulation of the VLPA produced a significant (P less than 0.01) increase in arterial blood pressure (ABP), a significant (P less than 0.05) decrease in CBF, and a significant (P less than 0.01) increase in cerebrovascular resistance (CVR) in the cerebral cortex ipsilateral to the stimulated VLPA. The CBF was 52 +/- 3 (mean +/- S.E.M.) and 48 +/- 4 ml.min-1.(100 g)-1 before and during the chemical stimulation of VLPA; the CVR was 1.9 +/- 0.1 and 2.6 +/- 0.3 mmHg per ml.min-1.(100 g)-1 before and during the stimulation. In order to measure CBF at normotension, moderate hypotension was induced by controlled hemorrhage in another group of rats (n = 8). Unilateral chemical stimulation of the VLPA in these rats increased ABP but it remained within normotensive range. The CBFs of ipsilateral and contralateral cerebral cortices decreased significantly (P less than 0.05) from 57 +/- 14 to 41 +/- 9 and from 50 +/- 12 to 39 +/- 9 ml.min-1.(100 g)-1, respectively. The CVRs of ipsilateral and contralateral cortices increased significantly (P less than 0.05) from 2.6 +/- 0.6 to 3.5 +/- 0.8 and from 2.7 +/- 0.5 to 3.5 +/- 0.8 mmHg/[ml.min-1.(100 g)-1], respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Scopolamine-sensitive and resistant components of increase in cerebral cortical blood flow elicited by periaqueductal gray matter of rats

The present study attempted to evaluate the effects of inhibition of cortical muscarinic receptors on the increase in cortical blood flow (laser-Doppler flowmetry) elicited by chemical stimulation of the periaqueductal gray matter in 28 anesthetized rats with cervical cordotomy. A new device was introduced which allowed focal cortical superfusion with scopolamine, an antagonist for muscarinic receptors, without disturbing the temperature of an exposed cortical area under study. We found that although the flow increase was attenuated by scopolamine (31.6 micromol/l to 1 mmol/l) so applied, about one third of it was resistant to the treatment. Cortical muscarinic and non-muscarinic receptor mechanisms may thus subserve the mediation of the flow increase.

Vasopressin-induced pressor response elicited by electrical stimulation of solitary nucleus and dorsal motor nucleus of vagus of rat

Electrical stimulation of the solitary nucleus and dorsal motor nucleus of the vagus elicited a pressor response in vagotomized rat with the spinal cord cut at C1. The response was entirely accounted for by an increased release of vasopressin upon stimulation as evidenced by absence of response in rats pretreated with a vasopressin antagonist and in Brattleboro rats.