Cerebral Palsy

Activated JNK has been reported to be located in nucleus in mild cases of Alzheimer’s disease (AD), but is exclusively in cytoplasm in more advanced stages of AD and implicated in its pathogenesis, suggesting that activation and re-distribution of JNK correlates with the progress of AD. The present study was designed to investigate the role of JNK in intracerebroventricular streptozotocin (i.c.v. STZ) induced cognitive impairment and oxidative stress. Streptozotocin has been observed to impair learning and memory, increase oxidative-nitritive stress, induce cholinergic hypofunction and neuronal damage in rat brain. Chronic treatment with SP600125 from day 10 to 28 following i.c.v. STZ injections significantly improved spatial memory, attenuate oxidative-nitritive stress. In addition, significant increase in acetylcholinesterase activity and lactate dehydrogenase (LDH) levels was observed in the present model indicating cholinergic hypofunction and increase in neuronal cell damage. Whereas, SP600125 treatment significantly restored acetylcholinesterase activity and reduced LDH levels indicating restorative capacity of SP600125 with respect to cholinergic functions and preventing the neuronal damage. In line with previous report, the current study also supports the potential of JNK inhibition as a possible therapeutic strategy to ameliorate neurodegenerative disorders associated with oxidative stress and cognitive impairment. Copyright © 2010. Published by Elsevier Inc.

There is consensus that the left hemisphere plays a dominant role in language processing, but functional imaging studies have shown that the right as well as the left posterior inferior frontal gyri (pIFG) are activated when healthy right-handed individuals make phonological word decisions. Here we used online transcranial magnetic stimulation (TMS) to examine the functional relevance of the right pIFG for auditory and visual phonological decisions. Healthy right-handed individuals made phonological or semantic word judgements on the same set of auditorily and visually presented words while they received stereotactically guided TMS over the left, right or bilateral pIFG (n= 14) or the anterior left, right or bilateral IFG (n= 14). TMS started 100ms after word onset and consisted of four stimuli given at a rate of 10Hz and intensity of 90% of active motor threshold. Compared to TMS of aIFG, TMS of pIFG impaired reaction times and accuracy of phonological but not semantic decisions for visually and auditorily presented words. TMS over left, right or bilateral pIFG disrupted phonological processing to a similar degree. In a follow-up experiment, the intensity threshold for delaying phonological judgements was identical for unilateral TMS of left and right pIFG. These findings indicate that an intact function of right pIFG is necessary for accurate and efficient phonological decisions in the healthy brain with no evidence that the left and right pIFG can compensate for one another during online TMS. Our findings motivate detailed studies of phonological processing in patients with acute and chronic damage of the right pIFG. Copyright © 2010. Published by Elsevier Ltd.

The aim of our study was to investigate neuroprotective properties of shikonin, a naphthoquinone pigment isolated from the roots of the traditional Chinese herb Lithospermum erythrorhizon. In the present study, mice were divided randomly into sham, model, shikonin and edaravone-treated groups. Shikonin (50, 25, 12.5 mg/kg, i.g.) or maize oil was administered three times before ischemia and once at 2 h after the onset of ischemia. Mice were anesthetized with chloral hydrate and subjected to middle cerebral artery 2 h of occlusion and then 22 h of reperfusion. Different antioxidant assays were employed in order to evaluate the antioxidant activities of shikonin in vitro. Neurological deficit, infarct size, histopathology changes and oxidative stress markers were evaluated after 22 h of reperfusion. In comparison with model group, treatment with shikonin significantly decreased neurological deficit scores, infarct size, the levels of malondialdehyde(MDA), carbonyl and reactive oxygen species, and attenuated neuronal damage, up-regulated superoxide dismutase(SOD), catalase, glutathione peroxidase(GSH-Px) activities and reduced glutathione(GSH)/ glutathione disulfide (GSSG) ratio. Taken together, these results suggested that neuroprotective effects of shikonin against cerebral ischemia/reperfusion injury maybe attributed to its antioxidant effects. Copyright © 2010 Elsevier B.V. All rights reserved.

Both TLR4 and TLR2 participated in the mediation of the inflammatory injury in the process of partial cerebral ischemia/reperfusion. However, it still remains unclear whether a crosstalk exists between TLR2 and TLR4 in ischemic cerebral damage. In the present study, we investigated the effect of TLR4 signaling on TLR2 expression during mimic cerebral I/R in vitro. BV-2 cells were cultured and treated with ischemia/reperfusion, then transfected with the plasmid pEGFP-H1/TLR4-siRNA, the plasmid pEGFP-H1/control sequence-siRNA and the blank plasmid, respectively. Interestingly, the expression of TLR2 and TLR4 mRNA and protein, NF-kappaB p65 mRNA and supernatant TNF-alpha level were significantly higher in ischemia/reperfusion treated cells than those lack of ischemia/reperfusion treatment, and as compared with those in ischemia/reperfusion treated cells without transfection, no significant differences about the above mentioned gene and protein expression were found in the blank plasmid tranfected cells and the plasmid pEGFP-H1/control sequence-siRNA transfected cells respectively, while the expression levels in the plasmid pEGFP-H1/TLR4-siRNA transfected cells were significantly lower. Additionally, in order to determine the effects of pyrrolidinediethyldithiocarbamate (PDTC), an NF-kappaB inhibitor, on the TLR4-induced TLR2 expression in BV-2 cells treated with ischemia/reperfusion, it was found that TLR4 and TLR2 mRNA expressions in PDTC pretreated cells were significantly lower in comparison with normal saline pretreated cells and non-pretreated cells. The data suggested that TLR2 activation, signaled by TLR4 and regulated by NF-kappaB, might be directly involved play an important role in ischemia/reperfusion induced brain damage.

Spinal cord and brain injuries usually lead to cavity formation. The transplantation by combining stem cells and tissue engineering scaffolds has the potential to fill the cavities and replace the lost neural cells. Both chitosan and collagen have their unique characteristics. In this study, the effects of chitosan and collagen on the behavior of rat neural stem cells (at the neurosphere level) were tested in vitro in terms of cytotoxicity and supporting ability for stem cell survival, proliferation and differentiation. Under the serum-free condition, both chitosan membranes and collagen gels had low cytotoxicity to neurospheres. That is, cells migrated from neurospheres, and processes extended out from these neurospheres and the differentiated cells. Compared with the above two materials, chitosan-collagen membranes were more suitable for the co-culture with rat neural stem cells, because, except for low cytotoxicity and supporting ability for the cell survival, in this group, a large number of cells were observed to migrate out from neurospheres, and the differentiating percentage from neurospheres into neurons was significantly increased. Further modification of chitosan-collagen membranes may shed light on in vivo nerve regeneration by transplanting neural stem cells.

Tissue-type plasminogen activator (t-PA) administration has been approved for treating acute ischemic stroke, but delayed treatment is associated with increased risk of cerebral hemorrhage and brain injury. t-PA, a serine proteinase, converts plasminogen to plasmin. Plasmin participates not only in the degradation of fibrin, causing clot lysis, but also in the degradation of various extracellular matrix proteins, either directly or via the activation of matrix metalloproteinase (MMPs). We established an animal stroke model and observed a phenomenon of spontaneous rethrombosis and thrombolysis in the cerebral vessels after vessel damage. Endogenous t-PA protected brain damage by recanalization, but the protective effect deteriorated when the occluded vessels were not reopened. On studying intracranial hemorrhage (ICH) induced by t-PA treatment of ischemic stroke, we observed that MMP-3 is relatively important for the enhanced ICH induced by t-PA. MMP-3 was upregulated by t-PA in endothelial cells, but the upregulation was prevented by the inhibition of either low-density lipoprotein receptor-related protein (LRP) or nuclear factor kappa-B (NF-kappaB) activation. Thus, t-PA causes ICH via MMP-3 induction in endothelial cells, which is regulated through the LRP/NF-kappaB pathway, and could be targeted to improve the therapeutic efficacy of t-PA for acute ischemic stroke.

BACKGROUND AND PURPOSE: Aneurysmal subarachnoid hemorrhage (aSAH) is a medical emergency characterized by the accumulation of blood in the subarachnoid space surrounding the brain. The acute treatment of aSAH is well documented but less is known about the long-term effects of aSAH on cognition and day-to-day functioning. METHODS: We reviewed all studies in the past 10 years that have focused on the effects of aSAH on cognition and day-to-day functioning. RESULTS: Sixty-one empirical studies examining cognitive and functional outcome in patients with aSAH met inclusion criteria. Survivors of aSAH commonly experience deficits in memory, executive function, and language. These cognitive impairments interact to affect patients’ day-to-day functioning, including activities of daily living, instrumental activities of daily living, return to work, and quality of life. Deficits in cognition and day-to-day functioning are further compounded by depression, anxiety, fatigue, and sleep disturbances. CONCLUSIONS: Much remains to be learned about the brain changes underlying cognitive and functional deficits, including the role of diffuse brain damage and secondary complications like vasospasm and elevated intracranial pressure. A consideration of these issues is necessary to obtain a better understanding of how aSAH affects cognition and day-to-day functioning in the long-term.

ABSTRACT: BACKGROUND: Cerebral ischemia/reperfusion injury is a common secondary effect of cardiac arrest which is largely responsible for postresuscitative mortality. Therefore development of therapies which restore and protect the brain function after cardiac arrest is essential. Methylene blue (MB) has been experimentally proven neuroprotective in a porcine model of global ischemia-reperfusion in experimental cardiac arrest. However, no comprehensive analyses have been conducted at gene expression level. METHODS: Pigs underwent either untreated cardiac arrest (CA) or CA with subsequent cardiopulmonary resuscitation (CPR) accompanied with an infusion of saline or an infusion of saline with MB. Genome-wide transcriptional profiling using the Affymetrix porcine microarray was performed to 1) gain understanding of delayed neuronal death initiation in porcine brain during ischemia and after 30, 60 and 180 min following reperfusion, and 2) identify the mechanisms behind the neuroprotective effect of MB after ischemic injury (at 30, 60 and 180 min). RESULTS: Our results show that restoration of spontaneous circulation (ROSC) induces major transcriptional changes related to stress response, inflammation, apoptosis and even cytoprotection. In contrast, the untreated ischemic and anoxic insult affected only few genes mainly involved in intra-/extracellular ionic balance. Furthermore, our data show that the neuroprotective role of MB is diverse and fulfilled by regulation of the expression of soluble guanylate cyclase and biological processes accountable for inhibition of apoptosis, modulation of stress response, neurogenesis and neuroprotection. CONCLUSIONS: Our results support that MB could be a valuable intervention and should be investigated as a therapeutic agent against neural damage associated with I/R injury induced by cardiac arrest.

Object Falls are the most common environmental setting for closed head injuries in children between 2 and 4 years of age. The authors previously found that toddlers had fewer skull fractures and scalp/facial soft-tissue injuries, and more frequent altered mental status than infants for the same low-height falls (</=3 ft). Methods To identify potential age-dependent mechanical load factors that may be responsible for these clinical findings, the authors created an instrumented dummy representing an 18-month-old child using published toddler anthropometry and mechanical properties of the skull and neck, and they measured peak angular acceleration during low-height falls (1, 2, and 3 ft) onto carpet pad and concrete. They compared these results from occiput-first impacts to previously obtained values measured in a 6-week-old infant dummy. Results Peak angular acceleration of the toddler dummy head was largest in the sagittal and horizontal directions and increased significantly (around 2-fold) with fall height between 1 and 2 ft. Impacts onto concrete produced larger peak angular accelerations and smaller impact durations than those onto carpet pad. When compared with previously measured infant drops, toddler head accelerations were more than double those of the infant from the same height onto the same surface, likely contributing to the higher incidence of loss of consciousness reported in toddlers. Furthermore, the toddler impact forces were larger than those in the infant, but because of the thicker toddler skull, the risk of skull fracture from low-height falls is likely lower in toddlers compared with infants. Conclusions If similar fracture limits and brain tissue injury thresholds between infants and toddlers are assumed, it is expected that for impact events, the toddler is likely less vulnerable to skull fracture but more vulnerable to neurological impairment compared with the infant.

Electrical injuries currently remain a worldwide problem. These injuries are responsible for considerable morbidity and mortality, but are usually preventable with simple safety measures. A retrospective study was undertaken of deaths due to electrocution that occurred over a five-year period from January 2002 to December 2006. The bodies were autopsied at the Department of Forensic Medicine, Coimbatore Medical College and Hospital, Coimbatore, Tamil Nadu, India. A total of 118 cases were identified and all were accidental: 107 males (91%) and 11 females (9%) (male:female ratio = 9.72). The majority of deaths occurred in the 21-30 year age group (n = 57, 48%). Most deaths (n = 98; 83%) were due to low-voltage circuits (< 1000 V); a minority were due to high voltages (n = 20, 17%). Domestic accidents were responsible in 73 cases (61.86%). Deaths were caused most frequently by touching an electric wire (n = 62; 52.54%). Most deaths occurred in the summer (n = 50; 42%) with the lowest number of deaths occurring in winter. There was no electrical contact mark present in eight cases (6.7%). One hundred and four cases (88%) were dead on arrival at hospital. The most common cause of death was cardiac arrest, followed by septicaemia and renal failure. Congestion of the brain and oedematous lungs were frequent non-specific postmortem findings.