Global brain delivery of neuroligin 2 gene ameliorates seizures in a mouse model of epilepsy.

Background: Despite the increasing availability of effective drugs, around one-third of patients with epilepsy are still resistant to pharmacotherapy. Gene therapy has been suggested as a plausible approach to achieve seizure control, in particular for patients with focal epilepsy. Because seizures develop across wide spans of the brain in many forms of epilepsy, global delivery of the vectors is necessary to tackle such generalized seizures.

Hippocampal GAD67 Transduction Using rAAV8 Regulates Epileptogenesis in EL Mice.

Gene therapy has been employed as a therapeutic approach for intractable focal epilepsies. Considering the potential of focal GABAergic neuromodulation in regulating epileptogenesis, the GABA-producing enzyme, γ-aminobutyric acid decarboxylase 67 (GAD67), is highly suitable for epilepsy therapy. The EL/Suz (EL) mouse is a model of multifactorial temporal lobe epilepsy.

Recovery of brain abscess-induced stuttering after neurosurgical intervention.

Stuttering occurs in approximately 5% of all children and 1% of adults. One type, neurogenic stuttering, is usually attributable to strokes or other structural damages to the brain areas that are responsible for language fluency. Here, we present the first case of neurogenic stuttering caused by a brain abscess.

Morphological changes indicative of brain hemisphere development and handedness in fixed brains and on CT/MRI images.

We measured the lengths of some parts of the right and left hemispheres (HEs) in 70 formalin-fixed brains and on 15 computed tomography/magnetic resonance imaging (CT/MRI) images (7 left-handed and 8 right-handed cases) to clarify the morphological changes indicating which HE developed earlier and handedness. In many cases of the fixed brains, 1) the distance from the frontal pole to the occipital pole was longer in the left HE than in the right HE, 2) the distance from the middle plane to the lateral-most portion of the HE was wider in the right HE than in the left HE, 3) the left occipital pole elongated more posteriorly and covered the right occipital pole, and 4) the volume of each HE was nearly the same. The results indicate that the left HE develops and grows slightly earlier in the larger semi-cranium (half of the cranium) than the right HE which develops later in the smaller semi-cranium.

A Case of Dural Arteriovenous Fistula in the Falx Cerebri: Case Report and Review of the Literature.

A 67-year-old man presented with consciousness disturbance and right hemiparesis. Computed tomography (CT) scan showed an intracerebral hematoma with two enhanced vascular lesions. Digital subtraction angiography revealed the dural arteriovenous fistula (dAVF) in the falx cerebri which was supplied by both bilateral middle meningeal arteries and left pericallosal artery and drained into both the superior sagittal sinus and the vein of Galen via the posterior callosal vein accompanied by two venous pouches.

Cutaneous invasive aspergillosis in a patient with glioblastoma receiving long-term temozolomide and corticosteroid therapy.

Glioblastoma is an aggressive brain tumor that requires multidisciplinary treatment including adjuvant radiotherapy, chemotherapy, and adjunct corticosteroids. Temozolomide is a commonly used chemotherapy drug and frequently causes lymphocytopenia. We describe the case of a 67-year-old woman with cutaneous invasive aspergillosis who had received long-term temozolomide and corticosteroid therapy for glioblastoma.

Determination of epileptic focus side in mesial temporal lobe epilepsy using long-term noninvasive fNIRS/EEG monitoring for presurgical evaluation.

Noninvasive localization of an epileptogenic zone is a fundamental step for presurgical evaluation of epileptic patients. Here, we applied long-term simultaneous functional near-infrared spectroscopy (fNIRS)/electroencephalogram (EEG) monitoring for focus diagnosis in patients with mesial temporal lobe epilepsy (MTLE). Six MTLE patients underwent long-term (8-16 h per day for 4 days) fNIRS/EEG monitoring for the occurrence of spontaneous seizures.

Direct cortical hemodynamic mapping of somatotopy of pig nostril sensation by functional near-infrared cortical imaging (fNCI).

Functional near-infrared spectroscopy (fNIRS) is a neuroimaging technique for the noninvasive monitoring of human brain activation states utilizing the coupling between neural activity and regional cerebral hemodynamics. Illuminators and detectors, together constituting optodes, are placed on the scalp, but due to the presence of head tissues, an inter-optode distance of more than 2.5cm is necessary to detect cortical signals.

Language-specific cortical activation patterns for verbal fluency tasks in Japanese as assessed by multichannel functional near-infrared spectroscopy.

In Japan, verbal fluency tasks are commonly utilized as a standard paradigm for neuropsychological testing of cognitive and linguistic abilities. The Japanese "letter fluency task" is a mora/letter fluency task based on the phonological and orthographical characteristics of the Japanese language. Whether there are similar activation patterns across languages or a Japanese-specific mora/letter fluency pattern is not certain.

Evoked potential mapping of the rostral region by frameless navigation system in Mexican hairless pig.

There is an increasing need for a pig model for use in functional brain studies, but a system for determining precise stereotactic coordinates has yet to be developed. Thus, we devised a frameless navigation system for stereotactic positioning, and measured coordinates for the rostral region and the primary somatosensory cortex in the pig brain. Raw coordinates for somatic evoked potential recordings were obtained by passive optical tracking.

Multichannel fNIRS assessment of overt and covert confrontation naming.

Confrontation naming tasks assess cognitive processes involved in the main stage of word production. However, in fMRI, the occurrence of movement artifacts necessitates the use of covert paradigms, which has limited clinical applications. Thus, we explored the feasibility of adopting multichannel functional near-infrared spectroscopy (fNIRS) to assess language function during covert and overt naming tasks.

Zinc-dependent multi-conductance channel activity in mitochondria isolated from ischemic brain.

Transient global ischemia is a neuronal insult that induces delayed cell death. A hallmark event in the early post-ischemic period is enhanced permeability of mitochondrial membranes. The precise mechanisms by which mitochondrial function is disrupted are, as yet, unclear.

Blockade of calcium-permeable AMPA receptors protects hippocampal neurons against global ischemia-induced death.

Transient global or forebrain ischemia induced experimentally in animals can cause selective, delayed neuronal death of hippocampal CA1 pyramidal neurons. A striking feature is a delayed rise in intracellular free Zn(2+) in CA1 neurons just before the onset of histologically detectable cell death. Here we show that alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs) at Schaffer collateral to CA1 synapses in postischemic hippocampus exhibit properties of Ca(2+)/Zn(2+)-permeable, Glu receptor 2 (GluR2)-lacking AMPARs before the rise in Zn(2+) and cell death.

Upregulation of GluR2 decreases intracellular Ca2+ following ischemia in developing gerbils.

Developing animals are known to be resistant to cerebral ischemia. To investigate the mechanisms by which developing animals exhibit ischemic resistance, we examined the changes in intracellular calcium ([Ca2+]i) after oxygen-glucose deprivation (OGD) using hippocampal slices from gerbils. We found that increases of [Ca2+]i in hippocampal CA1 neurons is significantly less after OGD in developing gerbils than in adults.

Ischemic preconditioning decreases intracellular zinc accumulation induced by oxygen-glucose deprivation in gerbil hippocampal CA1 neurons.

In normal gerbils, intracellular zinc ions ([Zn2+]i) and calcium ions ([Ca2+]i) accumulate in hippocampal CA1 neurons after global ischemia. We examined whether ischemic preconditioning modifies these changes in gerbil hippocampal slices. In normal slices, large increases in [Zn2+]i and [Ca2+]i were observed in the stratum radiatum of the CA1 area after oxygen-glucose deprivation.

Ischemic preconditioning: neuronal survival in the face of caspase-3 activation.

Apoptosis is an evolutionarily conserved process critical to tissue development and tissue homeostasis in eukaryotic organisms and, when dysregulated, causes inappropriate cell death. Global ischemia is a neuronal insult that induces delayed cell death with many features of apoptosis. Ischemic preconditioning affords robust protection of CA1 neurons against a subsequent severe ischemic challenge.

Ischemic insults derepress the gene silencer REST in neurons destined to die.

A subset of genes implicated in genetic and acquired neurological disorders encode proteins essential to neural patterning and neurogenesis. The gene silencing transcription factor neuronal repressor element-1 silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF) plays a critical role in elaboration of the neuronal phenotype. In neural progenitor and non-neural cells, REST acts by repression of a subset of neural genes important to synaptic plasticity and synaptic remodeling, including the AMPA receptor (AMPAR) subunit GluR2.

Differential effects of novel wasp toxin on rat hippocampal interneurons.

We studied the effects of a wasp toxin beta-pompilidotoxin (beta-PMTX) on rat hippocampal CA1 interneurons by the current-clamp technique. The firing patterns of pyramidal neurons and pyramidale interneurons were not affected by beta-PMTX, but in oriens and radiatum interneurons, beta-PMTX converted the action potentials to prolonged depolarizing potentials by slowing the inactivation of Na(+) channels. In lacunosum moleculare interneurons, beta-PMTX induced initial bursting spikes followed by block of succeeding spikes.

Ischemic preconditioning acts upstream of GluR2 down-regulation to afford neuroprotection in the hippocampal CA1.

Animals subjected to sublethal transient global ischemia (ischemic preconditioning) exhibit neuroprotection against subsequent global ischemia-induced neuronal death in the hippocampal CA1 (ischemic tolerance). The molecular mechanisms underlying ischemic tolerance are unclear. Here we report that ischemic preconditioning induced a small, transient down-regulation of GluR2 mRNA expression and greatly attenuated subsequent ischemia-induced GluR2 mRNA and protein down-regulation and neuronal death.