Increased Sestrin3 Contributes to Post-ischemic Seizures in the Diabetic Condition.

Seizures are among the most common neurological sequelae of stroke, and diabetes notably increases the incidence of post-ischemic seizures. Recent studies have indicated that Sestrin3 (SESN3) is a regulator of a proconvulsant gene network in human epileptic hippocampus. But the association of SESN3 and post-ischemic seizures in diabetes remains unclear.

Blood purification by nonselective hemoadsorption prevents death after traumatic brain injury and hemorrhagic shock in rats.

Background: Patients who sustain traumatic brain injury (TBI) and concomitant hemorrhagic shock (HS) are at high risk of high-magnitude inflammation which can lead to poor outcomes and death. Blood purification by hemoadsorption (HA) offers an alternative intervention to reduce inflammation after injury. We tested the hypothesis that HA would reduce mortality in a rat model of TBI and HS.

Reduced expression of IA channels is associated with post-ischemic seizures.

Purpose: Post-stroke seizures are considered as a major cause of epilepsy in adults. The pathophysiologic mechanisms resulting in post-stroke seizures are not fully understood. The present study attempted to reveal a new mechanism underlying neuronal hyperexcitability responsible to the seizure development after ischemic stroke.

Enhanced autophagy signaling in diabetic rats with ischemia-induced seizures.

Seizures are among the most common neurological sequelae of stroke, and ischemic insult in diabetes notably increases the incidence of seizures. Recent studies indicated that autophagy influences the outcome of stroke and involved in epileptogenesis. However, the association of autophagy and post-ischemic seizures in diabetes remains unclear.

Four-vessel occlusion model using aged male Wistar rats: a reliable model to resolve the discrepancy related to age in cerebral ischemia research.

Animal models of cerebral ischemia have typically been established and performed using young animals, even though cerebral ischemia (CI) affects primarily elderly patients. This situation represents a discrepancy that complicates the translation of novel therapeutic strategies for CI. Models of transient global CI using aged animals have demonstrated an apparent neuroprotective effect on CA1 hippocampal neurons; however, this effect is not completely understood.

Toll-like receptor 4 is associated with seizures following ischemia with hyperglycemia.

Seizures are a common sequel of cerebral ischemia, and hyperglycemia markedly increases the onset of seizures following an ischemic insult. However, the underlying mechanism of seizures is unclear. The toll-like receptor 4 (TLR4) pathway is known to be involved in temporal lobe epilepsy.

Reduced expression of IA channels is associated with postischemic seizures in hyperglycemic rats.

Poststroke seizures are considered to be the major cause of epilepsy in the elderly. The mechanisms of poststroke seizures remain unclear. A history of diabetes mellitus has been identified as an independent predictor of acute poststroke seizures in stroke patients.

A novel growth-promoting pathway formed by GDNF-overexpressing Schwann cells promotes propriospinal axonal regeneration, synapse formation, and partial recovery of function after spinal cord injury.

Descending propriospinal neurons (DPSN) are known to establish functional relays for supraspinal signals, and they display a greater growth response after injury than do the long projecting axons. However, their regenerative response is still deficient due to their failure to depart from growth supportive cellular transplants back into the host spinal cord, which contains numerous impediments to axon growth. Here we report the construction of a continuous growth-promoting pathway in adult rats, formed by grafted Schwann cells overexpressing glial cell line-derived neurotrophic factor (GDNF).

Alteration of neuronal activity after digit amputation in rat anterior cingulate cortex.

Phantom limb pain is experienced by nearly 50 - 80% of the patients following limb amputation. The anterior cingulate cortex (ACC) is a part of the limbic system that is an essential component in mediating the affective and emotional component of pain responses. To explore the role of ACC in the phantom limb pain, we recorded evoked excitatory postsynaptic potentials (EPSPs), cortical network activity and electrophysiological properties of pyramid neurons in adult rat ACC before and after a third hind paw digit amputation using in vivo intracellular or extracellular recording and staining techniques.

Thrombospondin-4 contributes to spinal sensitization and neuropathic pain states.

Neuropathic pain is a common cause of pain after nerve injury, but its molecular basis is poorly understood. In a post-gene chip microarray effort to identify new target genes contributing to neuropathic pain development, we report here the characterization of a novel neuropathic pain contributor, thrombospondin-4 (TSP4), using a neuropathic pain model of spinal nerve ligation injury. TSP4 is mainly expressed in astrocytes and significantly upregulated in the injury side of dorsal spinal cord that correlates with the development of neuropathic pain states.

Whole-cell patch-clamp recordings on spinal cord slices.

Whole-cell patch-clamp recording technique is a powerful tool to study intrinsic membrane properties and synaptic interactions in the spinal cord. Spinal cord slice is an idea preparation for electrophysiological studies under physiological and pharmacological manipulation that is difficult to perform in an in vivo preparation. Depending on experimental purposes, the extracellular and intracellular environment of neurons can be easily controlled during whole-cell recording to isolate membrane conductance of interest and to manipulate its modulation, which is important for addressing cellular mechanisms under particular physiological and pathological conditions.

Moderate traumatic brain injury causes acute dendritic and synaptic degeneration in the hippocampal dentate gyrus.

Hippocampal injury-associated learning and memory deficits are frequent hallmarks of brain trauma and are the most enduring and devastating consequences following traumatic brain injury (TBI). Several reports, including our recent paper, showed that TBI brought on by a moderate level of controlled cortical impact (CCI) induces immature newborn neuron death in the hippocampal dentate gyrus. In contrast, the majority of mature neurons are spared.

Alterations of A-type potassium channels in hippocampal neurons after traumatic brain injury.

Traumatic brain injury (TBI) is associated with cognitive deficits, memory impairment, and epilepsy. Previous studies have reported neuronal loss and neuronal hyperexcitability in the post-traumatic hippocampus. A-type K+ currents (I(A)) play a critical role in modulating the intrinsic membrane excitability of hippocampal neurons.

Downregulation of hippocampal GABA after hypoxia-induced seizures in neonatal rats.

This study aims to determine the expression of Gamma-aminobutyric acid (GABA) following hypoxia in neonatal rats and explore how it may increase susceptibility to epilepsy later in life. A modified model of neonatal hypoxia-induced epileptic susceptibility was simulated by 17 min of hypoxia (5% O(2) and 95% N(2)) in postnatal day (P) 10 rats. Hippocampal glutamate decarboxylase (GAD) and parvalbumin (PV) during the development with or without hypoxia were examined using immunohistochemistry.

Up-regulation of A-type potassium currents protects neurons against cerebral ischemia.

Excitotoxicity is the major cause of many neurologic disorders including stroke. Potassium currents modulate neuronal excitability and therefore influence the pathological process. A-type potassium current (I(A)) is one of the major voltage-dependent potassium currents, yet its roles in excitotoxic cell death are not well understood.

Contribution of Ih to neuronal damage in the hippocampus after traumatic brain injury in rats.

Traumatic brain injury (TBI) causes selective neuronal damage in the hippocampus; however, the underlying mechanisms are still unclear. Post-traumatic alterations of ion channel activity, which actively regulate neuronal excitability and thus impact on excitotoxicity, may be involved in TBI-induced neuronal injury. Here we report that hyperpolarization-activated cation current (I(h)) contributes to the distinct vulnerability of hippocampal neurons in TBI.

Increased GAD expression in the striatum after transient cerebral ischemia.

Striatum is one of the brain regions that are highly sensitive to transient cerebral ischemia. Most of the striatal neurons die shortly after ischemia but interneurons including large aspiny (LA) neurons survive the same insult. Previous studies have shown that inhibitory synaptic transmission is enhanced in LA neurons after ischemia.

Partial epilepsy with antecedent febrile seizures and seizure aggravation by antiepileptic drugs: associated with loss of function of Na(v) 1.1.

Purpose: Generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy in infancy (SMEI) are associated with sodium channel α-subunit type-1 gene (SCN1A) mutations. Febrile seizures and partial seizures occur in both GEFS+ and SMEI; sporadic onset and seizure aggravation by antiepileptic drugs (AEDs) are features of SMEI. We thus searched gene mutations in isolated cases of partial epilepsy with antecedent FS (PEFS+) that showed seizure aggravations by AEDs.

Activation of Akt/FoxO signaling pathway contributes to induction of neuroprotection against transient global cerebral ischemia by hypoxic pre-conditioning in adult rats.

It is well established that pre-conditioning protects neuronal injury against ischemia. However, the molecular mechanisms underlying ischemic tolerance are not completely understood. The purpose of the present study was to investigate the role of Akt/forkhead transcription factor, class O (FoxO) pathway in hypoxic pre-conditioning (HPC) using a newly developed HPC to transient global cerebral ischemia (tGCI) model in adult rats.

Characterization of the highly regulated antigen BBA05 in the enzootic cycle of Borrelia burgdorferi.

Dramatic alteration of surface lipoprotein profiles is a key strategy that Borrelia burgdorferi, the Lyme disease pathogen, has evolved for adapting to the diverse environments of arthropod and mammalian hosts. Several of these differentially expressed lipoproteins have been shown to play important roles in the enzootic cycle of B. burgdorferi.

Excitatory roles of protein kinase C in striatal cholinergic interneurons.

Protein kinase C (PKC) plays critical roles in neuronal activity and is widely expressed in striatal neurons. However, it is not clear how PKC activation regulates the excitability of striatal cholinergic interneurons. In the present study, we found that PKC activation significantly inhibited A-type potassium current (I(A)), but had no effect on delayed rectifier potassium currents.

Enhanced pre-synaptic glutamate release in deep-dorsal horn contributes to calcium channel alpha-2-delta-1 protein-mediated spinal sensitization and behavioral hypersensitivity.

Nerve injury-induced expression of the spinal calcium channel alpha-2-delta-1 subunit (Cavalpha2delta1) has been shown to mediate behavioral hypersensitivity through a yet identified mechanism. We examined if this neuroplasticity modulates behavioral hypersensitivity by regulating spinal glutamatergic neurotransmission in injury-free transgenic mice overexpressing the Cavalpha2delta1 proteins in neuronal tissues. The transgenic mice exhibited hypersensitivity to mechanical stimulation (allodynia) similar to the spinal nerve ligation injury model.

Diversity and fluctuation of spine morphology in CA1 pyramidal neurons after transient global ischemia.

Dendritic spines form postsynaptic components of excitatory synapses in CA1 pyramidal neurons and play a key role in excitatory signal transmission. Transient global ischemia is thought to induce excitotoxicity that triggers delayed neuronal death in the CA1 region. However, the mechanism underlying structural changes of excitatory synapses after ischemia is not completely understood.

Transient cerebral ischemia increases CA1 pyramidal neuron excitability.

In human and experimental animals, the hippocampal CA1 region is one of the most vulnerable areas of the brain to ischemia. Pyramidal neurons in this region die 2-3 days after transient cerebral ischemia whereas other neurons in the same region remain intact. The mechanisms underlying the selective and delayed neuronal death are unclear.

Dopamine D1-like receptors depress excitatory synaptic transmissions in striatal neurons after transient forebrain ischemia.

Background And Purpose: Spiny neurons in the neostriatum are highly vulnerable to ischemia. Despite an enormous body of research suggesting that dopamine is involved in ischemia-induced neuronal loss in the striatum, it remains unclear how dopamine interacts with the glutamatergic excitotoxicity that is widely accepted as a major cause of ischemic cell death. Our study was designed to investigate the effects of dopamine D1 receptor (D1R) activation on excitatory neurotransmission in postischemic striatal neurons.