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Traumatic brain injury (TBI) is one of the leading causes of death, long-term disability, and neurological impairments in children and young adults. TBI is associated with cognitive deficits and memory impairment. The Na+-K+-2Cl (NKCC) cotransporter contributes to the pathophysiology of common neurological disorders following TBI. The present study was designed to explore the potential therapeutic effect of bumetanide (a relatively specific inhibitor of NKCC1) on TBI-induced passive avoidance learning deficit in a rat model of controlled cortical impact (CCI) injury. Male rats were randomly divided into the following groups: (i) control animals that have undergone a sham surgical procedure, except for CCI delivery, (ii) TBI; received CCI delivery, (iii) Bumetanide plus TBI; received bumetanide 30 min before CCI delivery, (iv) TBI plus bumetanide; received bumetanide 30 min after CCI delivery. Passive avoidance learning (PAL) was assessed using a step-through apparatus on day 8 after TBI induction. CCI resulted in PAL deficits. The step-through latency in the acquisition trial (STLa) was significantly higher in the injured animals, and both pre-CCI and post-CCI bumetanide treatment decreased STLa. A decrease in step-through latency in the retention trial (STLr) and an increase in time spent in the dark compartment (TDC) during the retention test was observed in the injured animals. Both pre-CCI and post-CCI bumetanide treatment increased STLr and decreased TDC in injured animals. These findings suggest that bumetanide has a neuroprotective effect on TBI-induced memory impairment in rats and pharmacological inhibition of NKCC1 is protective against brain injury. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurological disease that slowly causing memory impairments with no effective treatment. We have recently reported that kisspeptin-13 (KP-13) ameliorates Aβ toxicity-induced memory deficit in rats. Here, the possible cellular impact of kisspeptin receptor activation in a rat model of the early stage AD was assessed using whole-cell patch-clamp recording from CA1 pyramidal neurons and molecular approaches. Compared to neurons from the control group, cells from the Aβ-treated group displayed spontaneous and evoked hyperexcitability with lower spike frequency adaptation. These cells had also a lower sag ratio in response to hyperpolarizing prepulse current delivered before a depolarizing current injection. Neurons from the Aβ-treated group exhibited short spike onset latency, lower rheobase and short utilization time compared with those in the control group. Furthermore, phase plot analysis of action potential showed that Aβ treatment affected the action potential features. These electrophysiological changes induced by Aβ were associated with increased expression of stromal interaction molecules (STIMs), particularly (STIM2) and decreased pCREB/CREB ratio. Treatment with KP-13 following Aβ injection into the entorhinal cortex, however, prevented the excitatory effect of Aβ on spontaneous and evoked neuronal activity, increased the latency of onset, enhanced the sag ratio, increased the rheobase and utilization time, and prevented the changes induced Aβ on spike parameters. In addition, the KP-13 application after Aβ treatment reduced the expression of STIMs and increased the pCREB/CREB ratio compared to those receiving Aβ treatment alone. In summary, these results provide evidence that activation of kisspeptin receptor may be effective against pathology of Aβ. • kisspeptin-13 prevented the Aβ-induced hyperexcitability in CA1 pyramidal neurons. • kisspeptin-13 treatment prevented Aβ-induced hippocampal overexpression of STIMs. • kisspeptin-13 treatment prevented the decreasing effect of Aβ on pCREB/CREB ratio. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is marked by neurobehavioral developmental deficits, potentially linked to disrupted neuron-glia interactions. The astroglia Kir4.1 channel plays a vital role in regulating potassium levels during neuronal activation, and mutations in this channel have been associated with ASD. This study investigates astroglia Kir4.1 as a regulator of neuronal excitability and behavioral abnormalities in rats with autistic-like traits induced by prenatal exposure to valproic acid (VPA). Whole-cell patch-clamp recordings were obtained from pyramidal neurons in the hippocampal CA1 region, showing that inhibition of Kir4.1 channels led to electrophysiological changes indicative of neuronal hyperexcitability, similar to that seen in VPA-exposed neurons. Specifically, there was increased input resistance and voltage threshold, alongside decreased time constant and rheobase. Behavioral assessments after 7 days of intrahippocampal PA6 (5 μg/mL/day) administration revealed significant social withdrawal, heightened anxiety, reduced exploration, and impaired recognition memory, underscoring the behavioral deficits linked to autism. While Kir4.1 inhibition affected excitability, it did not alter the output of CA1 pyramidal neurons in autistic-like rats. These findings emphasize the critical role of astroglia Kir4.1 channels in modulating neuronal excitability and associated behavioral impairments within the VPA-induced autism model, suggesting a promising target for future therapeutic interventions., (© 2025 Wiley Periodicals LLC.)