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  Citation statistics : Table of Contents
   2016| April-June  | Volume 2 | Issue 2  
    Online since July 13, 2016

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Pyruvate dehydrogenase complex in cerebral ischemia-reperfusion injury
Alexa Thibodeau, Xiaokun Geng, Lauren E Previch, Yuchuan Ding
April-June 2016, 2(2):61-66
DOI:10.4103/2394-8108.186256  PMID:30276274
Pyruvate dehydrogenase (PDH) complex is a mitochondrial matrix enzyme that serves a critical role in the conversion of anaerobic to aerobic cerebral energy. The regulatory complexity of PDH, coupled with its significant influence in brain metabolism, underscores its susceptibility to, and significance in, ischemia-reperfusion injury. Here, we evaluate proposed mechanisms of PDH-mediated neurodysfunction in stroke, including oxidative stress, altered regulatory enzymatic control, and loss of PDH activity. We also describe the neuroprotective influence of antioxidants, dichloroacetate, acetyl-L-carnitine, and combined therapy with ethanol and normobaric oxygen, explained in relation to PDH modulation. Our review highlights the significance of PDH impairment in stroke injury through an understanding of the mechanisms by which it is modulated, as well as an exploration of neuroprotective strategies available to limit its impairment.
  10 3,563 519
Wake-up stroke: Dawn of a new era
Konark Malhotra, David S Liebeskind
April-June 2016, 2(2):72-79
DOI:10.4103/2394-8108.186266  PMID:30276276
Wake-up stroke or stroke with unclear onset of symptoms is known to occur in one-fourth of ischemic stroke patients. These patients are not considered for thrombolytic therapy based on time designation of their symptom onset as per the current guidelines. Observational studies have investigated the pathophysiology and suggested actual onset of symptoms to be approximate to the awakening time for these patients. Use of advanced imaging modalities in these patients tends to identify favorable patient profiles for thrombolysis. Results of the ongoing trials will likely beckon a seminal juncture in stroke therapy and deliver critical modifications in the current treatment guidelines for thrombolysis in this substantial, yet neglected, group of stroke patients. In this article, we have reviewed the predisposing factors, preferred imaging modalities and various ongoing thrombolytic and endovascular trials to date for patients with unclear time of symptom onset or who wake up with stroke symptoms.
  8 5,349 929
Regeneration after stroke: Stem cell transplantation and trophic factors
Monica Chau, James Zhang, Ling Wei, Shan Ping Yu
April-June 2016, 2(2):86-94
DOI:10.4103/2394-8108.186279  PMID:30276278
Stroke is a leading cause of death and disability worldwide. However, there is only one Food and Drug Administration-approved drug for the treatment of ischemic stroke, i.e., tissue plasminogen activator, and its therapeutic window is limited to within 4.5 h after stroke. Since clinical trials for neuroprotection have failed to demonstrate efficacy, multipotent and pluripotent stem cell transplantations are viable candidates for stroke treatment by providing trophic factor support and/or cell replacement following injury. The goal of this review is to highlight the promise of stem cell transplantation as vehicles for trophic factor delivery. The beneficial effects of different stem cell types as transplants as well as ways to upregulate trophic factors in stem cells are described in this review. Stem cell transplantation has consistently shown beneficial effects in the ischemic stroke model, in part due to the beneficial factors that stem cells release around the stroke injury area, resulting in smaller infarct volumes and regeneration and functional recovery. Upregulation of beneficial factors in stem cells and neural progenitors before transplantation has been shown to be even more effective in treating the stroke injury than stem cells without upregulated factors. However, for both stem cells and genetic engineering, there remain many unanswered questions and potential for improvement. These include modifiable parameters such as the different stem cell types and different factors, as well as the various readouts for investigation, such as various in vivo effects, such as immune system modulation and enhancement of endogenous neurogenesis and angiogenesis.
  6 3,351 381
Rationale for ischemic conditioning to prevent stroke in patients with intracranial arterial stenosis
Sami Al Kasab, David C Hess, Marc I Chimowitz
April-June 2016, 2(2):67-71
DOI:10.4103/2394-8108.186260  PMID:30276275
Intracranial atherosclerotic arterial stenosis (ICAS) is one of the most common causes of stroke worldwide and is associated with particularly a high risk of recurrent stroke. Although aggressive medical management, consisting of dual antiplatelet therapy and intensive control of vascular risk factors, has improved the prognosis of patients with ICAS, subgroups of patients remain at very high risk of stroke. More effective therapies for these high-risk patients are urgently needed. One promising treatment is remote limb ischemic conditioning, which involves producing repetitive, transient ischemia of a limb by inflating a blood pressure cuff with the intention of protecting the brain from subsequent ischemia. In this study, we review the limitations of currently available treatments, discuss the potential mechanisms of action of ischemic conditioning, describe the preclinical and clinical data suggesting a possible role of ischemic conditioning in treating patients with ICAS, and outline the questions that still need to be answered in future studies of ischemic conditioning in subjects with ICAS.
  4 3,021 432
A rare case report of bilateral internal carotid artery hypoplasia in postpartum female: Clinical spectrum and role of various modalities in diagnosis
Bharat Gupta, Rohit Yadav, Manisha Singhal, Narendra Kadam, Kushal Baboo Gehlot, Rambir Singh
April-June 2016, 2(2):99-103
DOI:10.4103/2394-8108.186286  PMID:30276280
Congenital hypoplasia of bilateral internal carotid arteries (ICAs) is an extremely rare anomaly with less than 25 reported cases in literature till date. We present a case of a 30-year-old primigravida, who developed seizures and subsequently loss of consciousness just few minutes after the delivery of a healthy male child. To the best of our knowledge, this is the first case with bilateral ICA hypoplasia presenting in postpartum female who developed infarct in bilateral frontal region and subarachnoid hemorrhage (SAH). On a postpartum three-dimensional (3D) computed tomography (CT) angiography, bilateral ICA hypoplasia was confirmed and the manifestations of infarcts were probably the consequence of altered hemodynamics of pregnancy. In conclusion, a patient in her late pregnancy and postpartum period, having nonspecific cerebral symptoms or having suffered a cerebrovascular accident, should not only be evaluated for pregnancy or puerperium-related complications but also whenever possible a baseline screening with Doppler study of neck vessels and a noncontrast magnetic resonance imaging (MRI) angiography of neck and cerebral vessels should be performed to rule out congenital anomalies.
  1 3,179 296
Erratum: The role of shear stress and arteriogenesis in maintaining vascular homeostasis and preventing cerebral atherosclerosis.

April-June 2016, 2(2):104-104
DOI:10.4103/2394-8108.186288  PMID:30276281
  1 1,947 185
Clinical characteristics of 37 Chinese patients with myotonic dystrophy Type 1
Hui Lu, Yun Li, Mordechai Sadowsky, Yuwei Da
April-June 2016, 2(2):95-98
DOI:10.4103/2394-8108.186282  PMID:30276279
Objective: This study aims to investigate clinical characteristics of 37 Chinese patients with Myotonic dystrophy Type 1 (DM1). Methods: Main clinical features of these cases were analyzed, with a focus on multi-system involvements. Results: The median age of onset was 21.5 years, with a range from 3 to 45 years. Fourteen patients had a family history positive for DM1, whereas the other 23 were sporadic cases. Twenty-seven of the patients were male. The primary symptoms were myotonia and weakness with varying multi-system involvement including cardiac defects, cataracts, sleep disturbances, cholecystopathy, and peripheral neuropathy. Conclusions: This is the first report in China with the diagnosis of DM1 decisively confirmed by CTG expansion testing. Data from our study suggest that Chinese DM1 cases have different clinical characteristics compared with those of Caucasian cases, especially the prevalence of cardiac defects, cataracts, and sleep disturbances.
  1 2,553 253
Detrimental effects of physical inactivity on neurogenesis
Trenton Lippert, Nate Watson, Xunming Ji, Takao Yasuhara, Isao Date, Yuji Kaneko, Naoki Tajiri, Cesar V Borlongan
April-June 2016, 2(2):80-85
DOI:10.4103/2394-8108.186278  PMID:30276277
Patients diagnosed with neurological disorders exhibit a variety of physical and psychiatric symptoms, including muscle atrophy, general immobility, and depression. Patients who participate in physical rehabilitation at times show unexpected clinical improvement, which includes diminished depression and other stress-related behaviors. Regenerative medicine has advanced two major stem cell-based therapies for central nervous system (CNS) disorders, transplantation of exogenous stem cells, and enhancing the endogenous neurogenesis. The latter therapy utilizes a natural method of re-innervating the injured brain, which may mend neurological impairments. In this study, we examine how inactivity-induced atrophy, using the hindlimb suspension model, alters neurogenesis in rats. The hypothesis is that inactivity inhibits neurogenesis by decreasing circulation growth or trophic factors, such as vascular endothelial growth or neurotrophic factors. The restriction modifies neurogenesis and stem cell differentiation in the CNS, the stem cell microenvironment is examined by the trophic and growth factors, including stress-related proteins. Despite growing evidence revealing the benefits of "increased" exercise on neurogenesis, the opposing theory involving "physical inactivity," which simulates pathological states, continues to be neglected. This novel theory will allow us to explore the effects on neurogenesis by an intransigent stem cell microenvironment likely generated by inactivity. 5-bromo-2-deoxyuridine labeling of proliferative cells, biochemical assays of serum, cerebrospinal fluid, and brain levels of trophic factors, growth factors, and stress-related proteins are suggested identifiers of neurogenesis, while evaluation of spontaneous movements will give insight into the psychomotor effects of inactivity. Investigations devised to show how in vivo stimulation, or lack thereof, affects the stem cell microenvironment are necessary to establish treatment methods to boost neurogenesis in bedridden patients.
  1 3,092 254