1 This study investigated a local effect of cooling on the plantar skin blood flow (PSBF) of tetrodotoxin-treated rats by laser-Doppler flowmetry. 2 When the air temperature around the left foot was locally cooled from 25 to 101C, the PSBF of the left foot decreased. 3 The response was inhibited by the a-adrenoceptor antagonist phentolamine, the a 1 -adrenoceptor antagonist bunazosin, the a 2 -adrenoceptor antagonist RS79948, and bretylium and guanethidine that inhibit noradrenaline release from sympathetic nerves. Adrenalectomy of the rats did not affect the cooling-induced response. 4 The P2 purinoceptor antagonists suramin and PPADS also significantly suppressed the coolinginduced reduction of PSBF. However, the inhibitory effect of PPADS on the cooling-induced response was abolished after the treatment with phentolamine. Intra-arterial injections of ATPgS, a stable P2 purinoceptor agonist, at 251C caused a transient decrease in PSBF in a dose-dependent manner, which was significantly inhibited by phentolamine and guanethidine. 5 These results suggest a novel mechanism for local cooling-induced reduction of skin blood flow in vivo; moderate cooling of the skin induces the release of ATP, which stimulates presynaptic P2 purinoceptors on sympathetic nerve terminals and facilitates the release of noradrenaline, thereby causing contractions of skin blood vessels via the activation of a 1 -and a 2 -adrenoceptors.

AD could involve impairments in the vestibular control of balance. The VS test is useful for assessing the tendency to fall in AD. Impairment of VS in AD might arise from cerebral vestibular cortex impairment rather than comorbid peripheral vestibular disorders.

New Findings r What is the central question of this study?Brain hypoperfusion is a key factor triggering hypertension through activation of cardiovascular sympathetic vasomotor nerves. However, mechanisms of detecting brain hypoperfusion remain unclear. We hypothesized that the sympathetic premotor neurons in the rostral ventrolateral medulla (RVLM) can sense asphyxia and cause sympathoexcitation. r What is the main finding and its importance?Functionally identified RVLM sympathetic premotor neurons were excited by hypoxia but less so by hypercapnia, before and after blockade of synaptic transmission. The RVLM sympathetic premotor neurons can act as an important oxygen sensor during brain hypoxia/hypoperfusion, which may be important in maintaining sympathetic nerve discharge to support blood pressure and hence maintain brain perfusion.Brainstem hypoperfusion is a major excitant of sympathetic activity triggering hypertension, but the exact mechanisms involved remain incompletely understood. A major source of excitatory drive to preganglionic sympathetic neurons originates from the ongoing activity of premotor neurons in the rostral ventrolateral medulla (RVLM sympathetic premotor neurons). The chemosensitivity profile of physiologically characterized RVLM sympathetic premotor neurons during hypoxia and hypercapnia remains unclear. We examined whether physiologically characterized RVLM sympathetic premotor neurons can sense brainstem ischaemia intrinsically. We addressed this issue in a unique in situ arterially perfused preparation before and after a complete blockade of fast excitatory and inhibitory synaptic transmission. During hypercapnic hypoxia, respiratory modulation of RVLM sympathetic premotor neurons was lost, but tonic firing of most RVLM sympathetic premotor neurons was elevated. After blockade of fast excitatory and inhibitory synaptic transmission, RVLM sympathetic premotor neurons continued to fire and exhibited an excitatory firing response to hypoxia but not hypercapnia. This study suggests that RVLM sympathetic premotor neurons can sustain high levels of neuronal discharge when oxygen is scarce. The intrinsic ability of RVLM sympathetic premotor neurons to maintain responsivity to brainstem hypoxia is an important mechanism ensuring adequate arterial pressure, essential for maintaining cerebral perfusion in the face of depressed ventilation and/or high cerebral vascular resistance.

Koganezawa T, Terui N. Differential responsiveness of RVLM sympathetic premotor neurons to hypoxia in rabbits. Am J Physiol Heart Circ Physiol 292: H408 -H414, 2007. First published September 22, 2006; doi:10.1152/ajpheart.00881.2006.-To determine whether differential sympathetic nerve responses to hypoxia are explained by opposing effects of hypoxia upon sympathetic premotor neurons in the rostral ventrolateral medulla (RVLM), the cardiac sympathetic nerve and the renal sympathetic nerve were recorded in anesthetized and vagotomized rabbits. Renal sympathetic nerve was activated by the injection of sodium cyanide solution close to the bifurcation of the common carotid artery and/or by inhalation of hypoxic gas (3% oxygen-97% nitrogen). On the other hand, cardiac sympathetic nerve was inhibited by these stimuli. Barosensitive (inhibited by the stimulation of baroreceptor afferents) reticulospinal (antidromically activated by the stimulation of the spinal cord) neurons in the RVLM were divided into three groups according to their responses to hypoxic stimulation: neurons (Type I, n ϭ 25), the activity of which was inhibited by the injection of sodium cyanide solution close to the bifurcation of the common carotid artery and/or by inhalation of hypoxic gas, neurons (Type II, n ϭ 99), the activity of which was facilitated by the same stimulation, and neurons (Type III, n ϭ 11), the activity of which was not changed. These data indicated that the differential responses of cardiac and renal sympathetic nerves might be due to opposing effects of hypoxia on individual RVLM neurons. rostral ventrolateral medulla; cardiac sympathetic nerve; renal sympathetic nerve; chemoreceptor; regional different response PREMOTOR NEURONS for cardiovascular sympathetic nerves are located in the rostral ventrolateral medulla (RVLM) and have been called RVLM neurons (6,8,15). In almost all of the previous papers, the consensus is that RVLM neurons have tonic activity; receive information from baroreceptors, chemoreceptors, and other peripheral and central sources; and control vasoconstrictors and cardiac sympathetic nerve activity (CSNA) that control heart function and arterial pressure (15). Because the activities of cardiac accelerators and vasoconstrictors usually proceed in the same direction, for instance, in the case of the baroreceptor reflex, it has not been established whether a single premotor neuron innervates both of the preganglionic neurons of cardiac accelerators and vasoconstrictors or premotor neurons differentially control functionally different target neurons.Generally, a hypoxic stimulation is believed to excite sympathetic nerves, as well as visceral vasoconstrictors and muscle vasoconstrictors (12). However, it has been known that hypoxia produces different responses in sympathetic nerves. For example, hypoxia induces inactivation of cutaneous vasoconstrictors in cats, rats, and rabbits (7, 9). Furthermore, at least in the rabbit, hypoxia induces bradycardia through the inhibition of the activity of the cardiac sym...

Cell groups of the paramedian tract, which are located in the paramedian region of the lower brainstem, are eye-movement-related neurons that project to the cerebellar flocculus. Their inactivation produces downbeat nystagmus, which resembles eye movement disorders resulting from lesions of the cerebellar flocculus in animal experiments. Therefore, paramedian tract cells are assumed to fulfill an important function in ocular movement control, such as gaze-holding and maintaining vestibular balance. This paper presents a 50-year-old female who manifested downbeat nystagmus due to damage to the paramedian tract cells caused by a localized ischemic lesion in the medulla oblongata. We found that a paramedian medullary lesion-induced nystagmus, similar to that observed following floccular lesions, clearly indicates that a subgroup of paramedian tract cells projecting to the flocculus was impaired. This finding has important implications in considering a brainstem-cerebellar feedback loop involved in vestibulo-oculomotor controls, such as vestibular balance. Although there have been a few reports of downbeat nystagmus caused by lesions in the midline region of the lower brainstem, to our knowledge none report the occurrence of nystagmus due to a strictly localized medullar lesion, such as the one described here.