Tadachika Koganezawa

Local regulation of skin blood flow during cooling involving presynaptic P2 purinoceptors in rats

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 10°C, the PSBF of the left foot decreased. 3 The response was inhibited by the α‐adrenoceptor antagonist phentolamine, the α1‐adrenoceptor antagonist bunazosin, the α2‐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 cooling‐induced 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 ATPγS, a stable P2 purinoceptor agonist, at 25°C 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 α1‐and α2‐adrenoceptors.

Rhythmic activities of the sympatho-excitatory neurons in the medulla of rabbits: neurons controlling cutaneous vasomotion

Spontaneous activities of the reticulospinal neurons in the reticular formation of the rostroventral medulla, of the ear sympathetic nerve (ESNA) and of the renal sympathetic nerve (RSNA) were analyzed with regard to cardiac cycle- and respiration-related rhythm in the anesthetized, vagotomized and immobilized rabbits. A reticulospinal neuron that was concurrently excited with increase in the ESNA and/or reduction of the blood flow of the ear skin by electrical stimulation of the dorsomedial hypothalamus was tentatively named as a cutaneous sympatho-excitatory neuron (Cu neuron). More than half of the Cu neurons (13/22) had a respiration-related rhythmic activity as well as the ESNA. Activity of most of the Cu neurons (19/22) was not modulated with the frequency of the heartbeat and the ESNA had little or no cardiac cycle-related activity. Simultaneous recording shows that the degree of modulation (relative power of the power spectrum of the post event time histogram at the frequency of the respiration) of activity of the Cu neurons correlated with that of the ESNA. On the other hand, most (13/18) of the barosensitive sympatho-excitatory reticulospinal neurons in the rostral ventrolateral medulla (RVLM neurons) had both cardiac cycle- and respiration-related activity as well as the RSNA had. The Cu neurons were located at the medial sites to the location of the RVLM neurons. These results further showed that the Cu neurons controlled the cutaneous vasoconstrictor fibers and that the sympatho-excitatory neurons were located at the different sites in the ventral medulla according to their function.

Inhibitory synaptic modulation of Renshaw cell activity in the lumbar spinal cord of neonatal mice

In the mammalian spinal cord, Renshaw cells (RCs) are excited by axon collaterals of motoneurons (MNs), and in turn, provide recurrent inhibition of MNs. They are considered an important element in controlling the motor output. However, how RCs are modulated by spinal circuits during motor behaviors remains unclear. In this study, the physiological nature of inhibitory synaptic inputs to RCs in the lumbar segment during spontaneous motoneuronal activity was examined in the isolated spinal cord taken from glutamate decarboxylase 67-green fluorescent protein (GAD67-GFP) knock-in mouse neonates. Whole cell recordings of RCs in current-clamp mode showed that they receive phasic inhibition that could modulate the RC firing evoked by excitation of MNs. In voltage-clamp recording, we observed a barrage of spontaneous inhibitory postsynaptic currents (sIPSCs) mediated by glycine and/or GABA. These sIPSCs persisted in the presence of mecamylamine, a nicotinic receptor antagonist, indicating that excitation of other RCs by MN axon collaterals may not be essential for these inhibitory actions. Simultaneous recording of RC and the ventral root in the same segment showed that the RCs received inhibitory inputs when spontaneous MN firing occurred. Paired recordings of a RC and a MN showed that during the bursting activity in the ventral root, the magnitude of the RC sIPSCs and the magnitude of the excitatory inputs that MNs receive are highly correlated. These results indicate that RCs are modulated by inhibition that matches the MN excitation in timing and amplitude during motor behaviors.

The role of the RVLM neurons in the viscero-sympathetic reflex: A mini review

Neurons in the rostral ventrolateral medulla (RVLM neurons) receive inputs from various sources, including baroreceptors, and then regulate activity of sympathetic preganglionic neurons. Though RVLM neurons are assumed to mediate the viscero-sympathetic reflex, it has not been clarified yet. Here we give a brief overview of the participation of RVLM neurons in the viscero-sympathetic reflex. We conclude that RVLM neurons show excitatory and inhibitory responses to stimulation of sympathetic afferents and mediate multi-phase reflex responses of the sympathetic nerve.

Intrinsic chemosensitivity of rostral ventrolateral medullary sympathetic premotor neurons in the in situ arterially perfused preparation of rats

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. 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.

Downbeat nystagmus associated with damage to the medial longitudinal fasciculus of the pons: A vestibular balance control mechanism via the lower brainstem paramedian tract neurons

The paramedian tract (PMT) neurons, a group of neurons associated with eye movement that project into the cerebellar flocculus, are present in or near the medial longitudinal fasciculus (MLF) in the paramedian region of the lower brainstem. A 66-year-old man with multiple sclerosis in whom downbeat nystagmus appeared along with right MLF syndrome due to a unilateral pontomedullary lesion is described. In light of these findings, a possible schema for the vestibular balance control mechanism circuit of the PMT neurons via the flocculus is presented. Damage to the PMT neurons impaired the elective inhibitory control mechanism of the anterior semicircular canal neural pathway by the flocculus. This resulted in the appearance of anterior semicircular canal-dominant vestibular imbalance and the formation of downbeat nystagmus. From the pathogenesis of this vertical vestibular nystagmus, the action of the PMT neurons in the vestibular eye movement neuronal pathway to maintain vestibular balance was conjectured to be as follows. PMT neurons transmit vestibular information from the anterior semicircular canals to the cerebellum, forming a cerebellum/brainstem feedback loop. Vestibular information from that loop is integrated in the cerebellum, inhibiting only the anterior semicircular canal neuronal pathway via the flocculus and controlling vestibular balance.

Downbeat nystagmus due to a paramedian medullary lesion

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.

Vestibular Function Impairment in Alzheimer's Disease.

BACKGROUND Falls and fractures due to impaired balance in patients with Alzheimers disease (AD) have an adverse effect on the clinical course of the disease. OBJECTIVE To evaluate balance impairment in AD from the viewpoint of vestibular functional impairment. METHODS The subjects were 12 patients with AD, 12 dementia-free elderly adults, and 12 younger adults. Vestibular function was assessed using a stepping test, caloric nystagmus, and a visual suppression (VS) test. RESULTS The stepping test was abnormal in 9 of the 12 patients in the AD group. An abnormal stepping test was not associated with self-reported dizziness or tendency to fall. Significant VS abnormalities were present in the AD group. The suppression rate of VS was lower in AD patients with either a tendency to fall or constructional apraxia than in AD patients without either. The velocity of the rapid phase of caloric nystagmus before the VS test was similar in the AD group and the elderly control group. Significant abnormalities of both caloric nystagmus and VS were not present in either the elderly or the younger control groups. CONCLUSION 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.

Reticulospinal neurons inactivated by warming of the preoptic area and anterior hypothalamus of rabbits

To identify the premotor neurons for vasoconstrictors of the skin, activities of reticulospinal neurons in the rostroventral medulla, the ear sympathetic nerve (ESNA) and the renal sympathetic nerve (RSNA) were recorded in anesthetized and immobilized Japanese White or New Zealand White rabbits. Two groups of neurons were identified according to their responses to thermal stimulation of the preoptic area and the anterior hypothalamus (POAH) and to electrical stimulation of baroreceptor afferents, the aortic nerve (AN). Neurons (Type I neurons, n = 21) whose activity was inhibited by warm stimulation of the POAH but not inhibited by the AN stimulation were located in sites medial to the rostral ventrolateral medulla (RVLM). The other neurons (Type II neurons, n = 20) whose activity was not inhibited by warm stimulation of the POAH but inhibited by the AN stimulation were located in the RVLM. Because the time course of the inhibitory response of Type I neurons to warm stimulation of the POAH was very similar to that of the inhibitory response of the ESNA and activities of these neurons and the ESNA were not inhibited by the stimulation of the AN, it was suggested the Type I neurons might participate in regulation of activity of the vasoconstrictors of the ear skin. The Type II neurons are considered to be the barosensitive RVLM neurons that regulate systemic arterial pressure by controlling the activity of visceral or muscular sympathetic vasoconstrictors or cardiac sympathetic fibers.

Residual central nervous system damage due to organoarsenic poisoning

BACKGROUND Drinking well water contaminated with the organoarsenic compound diphenylarsinic acid (DPAA) causes central nervous system (CNS) disorders that improve within several years after last drinking such water. Subjective symptoms such as lightheadedness and dizziness appear to persist, however, suggesting CNS damage. We evaluated CNS damage due to DPAA by detecting abnormal eye movements. METHODS Subjects comprised 29 victims of exposure to DPAA in whom this substance had been detected in the nails. Investigations were performed more than 3years following cessation of DPAA exposure. Abnormal eye movements were monitored using electronystagmography. We analysed unpaired t-test between exposure subjects who exhibited upbeat nystagmus and those who did not. Upbeat nystagmus parameters were measured, and mean values were calculated. Associations between the properties of upbeat nystagmus and maximum concentrations of DPAA among DPAA exposure were also investigated. RESULTS Upbeat nystagmus was common among exposure victims, occurring in 23 of 29 subjects (79.0%). The subjects with upbeat nystagmus had significantly higher ratio than those without upbeat nystagmus in the points of subjective symptoms and DPAA concentration of drinking water (p<0.01). The slow-phase amplitude of upbeat nystagmus enlarged with increasing DPAA concentrations, showing a significant positive correlation (p<0.05). These findings suggest that the level of exposure to DPAA affects the properties of nystagmus. High-frequency pathological square-wave jerks (SWJ) were seen in 14 of 29 patients (48.0%), and mean SWJ frequency was 112.4±16.7/min. CONCLUSIONS Detection of abnormal ocular movements may be useful in evaluating residual/persistent/chronic CNS damage due to organoarsenic poisoning.