Brain research
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Voltage-gated Na+ channels in primary afferent neurons can be divided into tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) Na+ channels. Although previous studies have shown the acid modulation of TTX-R Na+ channels, the effect of acidic pH on tetrodotoxin-sensitive (TTX-S) Na+ channels is still unknown. Here we report the effect of acidic pH on TTX-S Na+ channels expressed in large-sized trigeminal ganglion (TG) neurons using a whole-cell patch clamp technique. ⋯ Acidic pH (pH 6.0) shifted both the activation and steady-state fast inactivation relationships of TTX-S Na+ channels toward depolarized potentials. However, acidic pH (pH 6.0) had no effect on use-dependent inhibition in response to high-frequency stimuli, development of inactivation, and accelerated the recovery from inactivation of TTX-S Na+ channels, suggesting that TTX-S Na+ channels in large-sized TG neurons are less sensitive to acidic pH. Given that voltage-gated Na+ channels play a pivotal role in the generation and conduction of action potentials in neural tissues, the insensitivity of TTX-S Na+ channels expressed in large-sized TG neurons to acidic pH would ensure transmission of innocuous tactile sensation from orofacial regions at acidic pH conditions.
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The blood-brain barrier (BBB) disruption during brain insults leads to vasogenic edema as one of the primary steps in the epileptogenic process. However, the signaling pathway concerning vasogenic edema formation has not been clarified. In the present study, status epilepticus (SE) resulted in vascular endothelial growth factor (VEGF) over-expression accompanied by loss of BBB integrity in the rat piriform cortex. ⋯ Furthermore, SB202190 (a p38 MAPK inhibitor) ameliorated vasogenic edema and VEGF over-expression induced by SE. These findings indicate that p38 MAPK/VEGF signaling pathway may be involved in BBB disruption following SE. Thus, we suggest that p38 MAPK/VEGF axis may be one of therapeutic targets for vasogenic edema in various neurological diseases.
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In animal models of tinnitus pathological neuronal activity has been demonstrated. Deep brain stimulation disrupts pathological neuronal activity and might therefore be a potential treatment for patients who suffer severely from tinnitus. In this study, the effect of DBS in the inferior colliculi is investigated in an animal model of tinnitus. ⋯ Hearing thresholds before and during DBS did not differ, indicating that hearing function is probably not impaired by electrical stimulation. In summary, this study shows that DBS of the inferior colliculi is effective in reducing behavioral signs of tinnitus in an animal model. Impaired hearing function could not be objectified as a side effect of stimulation.
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Our recent researches have identified increased expression of miR-21-5p in rats brain following traumatic brain injury (TBI), which protected against blood-brain barrier (BBB) damage. To further study the mechanism underlying the role of miR-21-5p on alleviating BBB damage after TBI, we performed the scratch injury model on cultured brain microvascular endothelial cells (BMVECs), which formed the microvascular endothelial barrier - an integral part of the highly specialized BBB. The expression level of miR-21-5p in BMVECs was observed to be increased after scratch injury, and could be further up-regulated by transfecting miR-21-5p mimics. ⋯ In addition, we also detected the activity of Ang-1/Tie-2 axis (associated with BBB stabilization) in BMVECs after scratch injury, and found that miR-21-5p can promote its activation. Taken together, miR-21-5p alleviates leakage of injured brain microvascular endothelial barrier through suppressing inflammation and apoptosis, while impacting the activities of NF-kB, Akt and Ang-1/Tie-2 signaling. Thus, miR-21-5p could be a potential therapeutic target for interventions of BBB damage after TBI.
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Thermoregulatory responses to lipopolysaccharide (LPS) are affected by modulators that increase (propyretic) or decrease (cryogenic) body temperature (Tb). We tested the hypothesis that central hydrogen sulfide (H2S) acts as a thermoregulatory modulator and that H2S production in the anteroventral preoptic region of the hypothalamus (AVPO) is increased during hypothermia and decreased during fever induced by bacterial lipopolysaccharide (LPS, 2.5mg/kg i.p.) in rats kept at an ambient temperature of 25°C. Deep Tb was recorded before and after pharmacological inhibition of the enzyme cystathionine β-synthase (CBS - responsible for H2S endogenous production in the brain) combined or not with LPS administration. ⋯ Intracerebroventricular (icv) microinjection of aminooxyacetate (AOA, a CBS inhibitor; 100 pmol) neither affected Tb nor basal PGD2 production during euthermia. In LPS-treated rats, AOA caused increased Tb values during hypothermia, along with enhanced PGD2 production. We conclude that the gaseous messenger H2S modulates hypothermia during endotoxic shock, acting as a cryogenic molecule.