Previous studies have indicated that electrical stimulation of the cerebellar fastigial nucleus in rats may reduce brain infarct size, increase the expression of Ku70 in cerebral ischemia/reperfusion area, and decrease the number of apoptotic neurons. However, the anti-apoptotic mechanism of Ku70 remains unclear. In this study, fastigial nucleus stimulation was given to rats 24, 48, and 72 hours before cerebral ischemia/reperfusion injury. Results from the electrical stim-ulation group revealed that rats exhibited a reduction in brain infarct size, a signiifcant increase in the expression of Ku70 in cerebral ischemia/reperfusion regions, and a decreased number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells. Double immunofluorescence staining revealed no co-localization of Ku70 with TUNEL-positive cells. However, Ku70 partly co-localized with Bax protein in the cytoplasm of rats with cerebral ischemia/reperfusion injury. These ifndings suggest an involvement of Ku70 with Bax in the cy-toplasm of rats exposed to electrical stimulation of the cerebellar fastigial nucleus, and may thus provide an understanding into the anti-apoptotic activity of Ku70 in cerebral ischemia/reperfu-sion injury.

Non-invasive brain stimulations mainly consist of repetitive transcranial magnetic stimulation and transcranial direct current stimulation. Repetitive transcranial magnetic stimulation exhib-its satisfactory outcomes in improving multiple sclerosis, stroke, spinal cord injury and cerebral palsy-induced spasticity. By contrast, transcranial direct current stimulation has only been studied in post-stroke spasticity. To better validate the effcacy of non-invasive brain stimulations in im-proving the spasticity post-stroke, more prospective cohort studies involving large sample sizes are needed.

3-N-butylphthalide is an effective drug for acute ischemic stroke. However, its effects on chronic cerebral ischemia-induced neuronal injury remain poorly understood. Therefore, this study li-gated bilateral carotid arteries in 15-month-old rats to simulate chronic cerebral ischemia in aged humans. Aged rats were then intragastrically administered 3-n-butylphthalide. 3-N-butylphtha-lide administration improved the neuronal morphology in the cerebral cortex and hippocampus of rats with chronic cerebral ischemia, increased choline acetyltransferase activity, and decreased malondialdehyde and amyloid beta levels, and greatly improved cognitive function. These findings suggest that 3-n-butylphthalide alleviates oxidative stress caused by chronic cerebral ischemia, improves cholinergic function, and inhibits amyloid beta accumulation, thereby im-proving cerebral neuronal injury and cognitive deifcits.

Activation of nuclear factor kappa B (NF-κB) is a hallmark of various central nervous system (CNS) pathologies. Neuron-speciifc inhibition of its transcriptional activator subunit RelA, also referred to as p65, promotes neuronal survival under a range of conditions, i.e., for ischemic or excitotoxic insults. In macro-and microglial cells, post-lesional activation of NF-κB triggers a growth-permissive program which contributes to neural tissue inlfammation, scar formation, and the expression of axonal growth inhibitors. Intriguingly, inhibition of such inducible NF-κB in the neuro-glial compartment, i.e., by genetic ablation of RelA or overexpression of a trans-dominant negative mutant of its upstream regulator IκBα, significantly enhances functional recovery and promotes axonal regeneration in the mature CNS. By contrast, depletion of the NF-κB subunit p50, which lacks transcriptional activator function and acts as a transcriptional repressor on its own, causes precocious neuronal loss and exacerbates axonal degeneration in the lesioned brain. Collectively, the data imply that NF-κB orchestrates a multicellular pro-gram in whichκB-dependent gene expression establishes a growth-repulsive terrain within the post-lesioned brain that limits structural regeneration of neuronal circuits. Considering these subunit-speciifc functions, interference with the NF-κB pathway might hold clinical potentials to improve functional restoration following traumatic CNS injury.

Traumatic brain injury (TBI) is the leading cause of death and disability of persons under 45 years old in the United States, affecting over 1.5 million individuals each year. It had been th ought that recovery from such injuries is severely limited due to the inability of the adult bra in to replace damaged neurons. However, recent studies indicate that the mature mammalian central nervous system (CNS) has the potential to replenish damaged neurons by proliferation and neuronal differentiation of adult neural stem/progenitor cells residing in the neurogenic regions in the brain. Furthermore, increasing evidence indicates that these endogenous stem/progenitor cells may play regenerative and reparative roles in response to CNS injuries or diseases. In support of this notion, heightened levels of cell proliferation and neurogenesis have been ob-served in response to brain trauma or insults suggesting that the brain has the inherent potential to restore populations of damaged or destroyed neurons. This review will discuss the potential functions of adult neurogenesis and recent development of strategies aiming at harnessing this neurogenic capacity in order to repopulate and repair the injured brain.

Stem cells have the remarkable potential to develop into many different cell types, essentially with-out limit to replenish other cells as long as the person or animal is still alive, offering immense hope of curing Alzheimer’s disease, repairing damaged spinal cords, treating kidney, liver and lung diseases and making damaged hearts whole. Until recently, scientists primarily worked with two kinds of stem cells from animals and humans:embryonic stem cells and non-embryonic“somatic”or“adult”stem cells. Recent breakthrough make it possible to convert or“reprogram”specialized adult cells to assume a stem stem-like cells with different technologies. The review will brielfy dis-cuss the recent progresses in this area.

To investigate the molecular mechanism underlying the neuroprotective effect of lithium on cells, in this study, we exposed SH-SY5Y cells to 0.5 mmol/L lithium carbonate (Li2CO2) for 25-50 weeks and then detected the expression levels of some neurobiology related genes and post-translational modifications of stress proteins in SH-SY5Y cells. cDNA arrays showed that pyruvate kinase 2 (PKM2) and calmodulin 3 (CaM 3) expression levels were signiifcantly down-regulated, phosphatase protein PP2A expression was lightly down-regulated, and casein kinase II (CK2), threonine/tyrosine phosphatase 7 (PYST2), and dopamine beta-hydroxylase (DBH) expression levels were signiifcantly up-regulated. Besides, western blot analysis of stress proteins (HSP27, HSP70, GRP78 and GRP94) showed an over-expression of two proteins:a 105 kDa protein which is a hyper-phosphorylated isoform of GRP94, and a 108 kDa protein which is a phosphorylated tetramer of HSP27. These results suggest that the neuroprotective effects of lithium are likely related to gene expressions and post-translational modiifcations of proteins cited above.

Houshiheisan is composed of wind-dispelling (chrysanthemun lfower, divaricate saposhnikovia root, Manchurian wild ginger, cassia twig, Szechwan lovage rhizome, and platycodon root) and deifciency-nourishing (ginseng, Chinese angelica, large-head atractylodes rhizome, Indian bread, and zingiber) drugs. In this study, we assumed these drugs have protective effects against cerebral ischemia, on neurovascular units. Houshiheisan was intragastrically administered in a rat model of focal cerebral ischemia. Hematoxylin-eosin staining, transmission electron microscopy, immu-nolfuorescence staining, and western blot assays showed that Houshiheisan reduced pathological injury to the ischemic penumbra, protected neurovascular units, visibly up-regulated neuronal nuclear antigen expression, and down-regulated amyloid precursor protein and amyloid-β42 expression. Wind-dispelling and deifciency-nourishing drugs maintained NeuN expression to varying degrees, but did not affect amyloid precursor protein or amyloid-β42 expression in the ischemic penumbra. Our results suggest that the compound prescription Houshiheisan effectively suppresses abnormal amyloid precursor protein accumulation, reduces amyloid substance depo-sition, maintains stabilization of the internal environment of neurovascular units, and minimizes injury to neurovascular units in the ischemic penumbra.

Activation of extracellular signal-regulated kinase 1/2 has been demonstrated in acute brain ischemia. We hypothesized that activated extracellular signal-regulated kinase 1/2 can protect hippocampal neurons from injury in a diabetic model after cerebral ischemia/reperfusion. In this study, transient whole-brain ischemia was induced by four-vessel occlusion in normal and diabetic rats, and extracellular signal-regulated kinase 1/2 inhibitor (U0126) was administered into diabetic rats 30 minutes before ischemia as a pretreatment. Results showed that the number of surviving neurons in the hippocampal CA1 region was reduced, extracellular signal-regulated kinase 1/2 phosphorylation and Ku70 activity were decreased, and pro-apoptotic Bax expression was upregulated after intervention using U0126. These ifndings demonstrate that inhibition of extracellular signal-regulated kinase 1/2 activity aggravated neuronal loss in the hippocampus in a diabetic rat after cerebral ischemia/reperfusion, further decreased DNA repairing ability and ac-celerated apoptosis in hippocampal neurons. Extracellular signal-regulated kinase 1/2 activation plays a neuroprotective role in hippocampal neurons in a diabetic rat after cerebral ischemia/reperfusion.

In the hours to weeks following traumatic spinal cord injuries (SCI), biochemical processes are initiated that further damage the tissue within and surrounding the initial injury site:a process termed secondary injury. Acrolein, a highly reactive unsaturated aldehyde, has been shown to play a major role in the secondary injury by contributing signiifcantly to both motor and sensory deif-cits. In particular, efforts have been made to elucidate the mechanisms of acrolein-mediated dam-age at the cellular level and the resulting paralysis and neuropathic pain. In this review, we will highlight the recent developments in the understanding of the mechanisms of acrolein in motor and sensory dysfunction in animal models of SCI. We will also discuss the therapeutic beneifts of using acrolein scavengers to attenuate acrolein-mediated neuronal damage following SCI.

OBJECTIVE:To evaluate the effectiveness and safety of ifliform needle acupuncture for poststroke depression, and to compare acupuncture with the therapeutic efifcacy of antidepressant drugs.
DATA RETRIEVAL:We retrieved data from the Chinese National Knowledge Infrastructure (1979-2012), Wanfang (1980-2012), VIP (1989-2012), Chinese Biomedical Literature (1975-2012), PubMed (1966-2012), Ovid Lww (-2012), and Cochrane Library (-2012) Database using the internet.
SELECTION CRITERIA:Randomized controlled trials on ifliform needle acupuncture versus antidepressant drugs for treatment of poststroke depression were included. Moreover, the in-cluded articles scored at least 4 points on the Jadad scale. Exclusion criteria:other acupuncture therapies as treatment group, not stroke-induced depression patients, score<4 points, non-ran-domized controlled trials, or animal trials.
MAIN OUTCOME MEASURES:These were the Hamilton Depression Scale scores, clinical ef-fective rate, Self-Rating Depression Scale scores, Side Effect Rating Scale scores, and incidence of adverse reaction and events.
RESULTS:A total of 17 randomized controlled clinical trials were included. Meta-analysis results displayed that after 4 weeks of treatment, clinical effective rate was better in patients treated with ifli-form needle acupuncture than those treated with simple antidepressant drugs [relative risk =1.11, 95%conifdence interval (CI):1.03-1.21, P=0.01]. At 6 weeks, clinical effective rate was similar between ifliform needle acupuncture and antidepressant drug groups. At 2 weeks after ifliform needle acupuncture, Hamilton Depression Scale (17 items) scores were lower than in the antide-pressant drug group (mean difference=-2.34, 95%CI:-3.46 to-1.22, P<0.000,1). At 4 weeks, Hamilton Depression Scale (24 items) scores were similar between ifliform needle acupuncture and antidepressant drug groups. Self-Rating Depression Scale scores were lower in filiform needle acupuncture group than in the antidepressant drug group. Side Effect Rating Scale was used in only two articles, and no meta-analysis was conducted. Safety evaluation of the 17 arti-cles showed that gastrointestinal tract reactions such as nausea and vomiting were very common in the antidepressant drug group. Incidence of adverse reaction and events was very low in the ifliform needle acupuncture group.
CONCLUSION:Early ifliform needle acupuncture for poststroke depression can perfectly con-trol depression. Filiform needle acupuncture is safe and reliable. Therapeutic effects of ifliform needle acupuncture were better than those of antidepressant drugs.

Many studies have examined motor impairments using voxel-based lesion symptom mapping, but few are reported regarding the corresponding relationship between cerebral cortex injury and lower limb motor impairment analyzed using this technique. This study correlated neuro-nal injury in the cerebral cortex of 16 patients with chronic stroke based on a voxel-based lesion symptom mapping analysis. Neuronal injury in the corona radiata, caudate nucleus and putamen of patients with chronic stroke could predict walking speed. The behavioral measure scores were consistent with motor deifcits expected after damage to the cortical motor system due to stroke. These ifndings suggest that voxel-based lesion symptom mapping may provide a more accurate prognosis of motor recovery from chronic stroke according to neuronal injury in cerebral motor cortex.

The brain is highly plastic after stroke or epilepsy;however, there is a paucity of brain plasticity investigation after traumatic brain injury (TBI). This mini review summarizes the most recent evidence of brain plasticity in human TBI patients from the perspective of advanced magnetic resonance imaging. Similar to other forms of acquired brain injury, TBI patients also demonstrat-ed both structural reorganization as well as functional compensation by the recruitment of other brain regions. However, the large scale brain network alterations after TBI are still unknown, and the ifeld is still short of proper means on how to guide the choice of TBI rehabilitation or treat-ment plan to promote brain plasticity. The authors also point out the new direction of brain plas-ticity investigation.