Resistance to tissue hypoxia is a robust fundamental adaptation to low oxygen supply, and represents a novel neuroscience problem with significance to mammalian physiology as well as human health. With the underlying mechanisms strongly conserved in evolution, the ability to resist tissue hypoxia in natural systems has recently emerged as an interesting model in mammalian physiology research to understand mechanisms that can be manipulated for the clinical management of stroke. The extraordinary ability to resist tissue hypoxia by the naked mole rat (NMR) indicates the presence of a unique mechanism that underlies the remarkable healthy life span and exceptional hypoxia resistance. This opens an interesting line of research into understanding the mechanisms employed by the naked mole rat (. Heterocephalus glaber) to protect the brain during hypoxia. In a series of studies, we first examined the presence of neuroprotection in the brain cells of naked mole rats (NMRs) subjected to hypoxic insults, and then characterized the expression of such neuroprotection in a wide range of time intervals. We used oxygen nutrient deprivation (OND), an in vitro model of resistance to tissue hypoxia to determine whether there is evidence of neuronal survival in the hippocampal (CA1) slices of NMRs that are subjected to chronic hypoxia. Hippocampus neurons of NMRs that were kept in hypoxic condition consistently tolerated OND right from the onset time of 5. h. This tolerance was maintained for 24. h. This finding indicates that there is evidence of resistance to tissue hypoxia by CA1 neurons of NMRs. We further examined the effect of hypoxia on metabolic rate in the NMR. Repeated measurement of metabolic rates during exposure of naked mole rats to hypoxia over a constant ambient temperature indicates that hypoxia significantly decreased metabolic rates in the NMR, suggesting that the observed decline in metabolic rate during hypoxia may contribute to the adaptive mechanism used by the NMR to resist tissue hypoxia. This work is aimed to contribute to the understanding of mechanisms of resistance to tissue hypoxia in the NMR as an important life-sustaining process, which can be translated into therapeutic interventions during stroke.

Resistance to tissue hypoxia is a robust fundamental adaptation to low oxygen supply, and represents a novel neuroscience problem with significance to mammalian physiology as well as human health. With the underlying mechanisms strongly conserved in evolution, the ability to resist tissue hypoxia in natural systems has recently emerged as an interesting model in mammalian physiology research to understand mechanisms that can be manipulated for the clinical management of stroke. The extraordinary ability to resist tissue hypoxia by the naked mole rat (NMR) indicates the presence of a unique mechanism that underlies the remarkable healthy life span and exceptional hypoxia resistance. This opens an interesting line of research into understanding the mechanisms employed by the naked mole rat (. Heterocephalus glaber) to protect the brain during hypoxia. In a series of studies, we first examined the presence of neuroprotection in the brain cells of naked mole rats (NMRs) subjected to hypoxic insults, and then characterized the expression of such neuroprotection in a wide range of time intervals. We used oxygen nutrient deprivation (OND), an in vitro model of resistance to tissue hypoxia to determine whether there is evidence of neuronal survival in the hippocampal (CA1) slices of NMRs that are subjected to chronic hypoxia. Hippocampus neurons of NMRs that were kept in hypoxic condition consistently tolerated OND right from the onset time of 5. h. This tolerance was maintained for 24. h. This finding indicates that there is evidence of resistance to tissue hypoxia by CA1 neurons of NMRs. We further examined the effect of hypoxia on metabolic rate in the NMR. Repeated measurement of metabolic rates during exposure of naked mole rats to hypoxia over a constant ambient temperature indicates that hypoxia significantly decreased metabolic rates in the NMR, suggesting that the observed decline in metabolic rate during hypoxia may contribute to the adaptive mechanism used by the NMR to resist tissue hypoxia. This work is aimed to contribute to the understanding of mechanisms of resistance to tissue hypoxia in the NMR as an important life-sustaining process, which can be translated into therapeutic interventions during stroke.

7,8-Dihydroxy-4-methylcoumarin (Dhmc) is a precursor in the synthesis of derivatives of 4-methyl coumarin, which has excellent radical scavenging properties. In this study, we investigated whether Dhmc protects against oxidative stress and ischemic brain injury. We found that Dhmc protected against glutamate toxicity in hippocampal HT-22 cells in a concentration-dependent manner in vitro. Dhmc inhibited glutamate-induced glutathione depletion and generation of reactive oxygen species, suggesting that Dhmc has an antioxidant effect. In addition, Dhmc inhibited glutamate-induced depletion of hippocalcin, a protein that buffers intracellular calcium and prevents calcium-induced cell death. In our in vivo studies, Dhmc reduced infarct volume in neonatal rats when administered 4 h after cerebral hypoxia/ischemia injury and attenuated the hypoxia/ischemia injury-induced decrease of hippocalcin expression in neonatal rats. Taken together, these results suggest that Dhmc prevents glutamate-induced toxicity by scavenging free radicals and regulating hippocalcin expression. Dhmc may represent a promising agent in the treatment of acute and chronic neurological disorders induced by oxidative stress.

Penetrating brain injury resulting from nail-gun use is a well-characterized entity, one that is increasing in frequency as nail guns become more powerful and more readily available to the public. We present a case and offer management strategies for a 50-year-old male with two intracranial penetrating nail gun injuries. Nail gun brain injuries are commonly intentionally self-inflicted. Suicide should be considered when straight nails cause wounds to the chest, head, or abdomen. The primary preoperative concern is formation of a traumatic pseudoaneurism, which prompts both preoperative and follow-up cerebral angiography. Surgery for combined intracranial and extracranial injury may require the collaborative expertise of colleagues from the fields of ophthalmology, otolaryngology, and oral maxillofacial surgery. A rational management strategy should permit these patients to be discharged with no additional injury.

Background: Previously, we had shown that elevation of cerebral perfusion pressure, using pressors, improved short-term outcomes after traumatic brain injury and hemorrhagic shock in swine. The current study evaluates outcomes after resuscitation with diaspirin cross-linked hemoglobin (DCLHb)-a hemoglobin-based oxygen carrier with pressor activity-in the same swine model of traumatic brain injury and hemorrhagic shock. Methods: Anesthetized and ventilated swine received traumatic brain injury via cortical fluid percussion (6-8 atm) followed by 45% blood volume hemorrhage. One hour later, animals were randomized to either a control group (SAL) resuscitated with normal saline equal to three times shed blood volume or to one of two experimental groups resuscitated with DCLHb. The two experimental groups consisted of a low-dose group, resuscitated with 250 mL of DCLHb (Hb1), and a high-dose group, resuscitated with 500 mL of DCLHb (Hb2). Animals were observed for 210 minutes postresuscitation. Outcomes evaluated were cerebral oxygenation by measuring partial pressure and saturation of oxygen in cerebrovenous blood; cerebral function by evaluating the preservation and magnitude of cerebrovascular carbon dioxide reactivity; and brain structural damage by semiquantitatively assessing beta amyloid precursor protein positive axons. Results: Postresuscitation, cerebral perfusion pressure was higher in the DCLHb groups (p < 0.05, Hb1 and Hb2 vs. SAL), and intracranial pressure was lower in the Hb2 group (p < 0.05 vs. SAL). Cerebrovenous oxygen level was similar in all groups (p > 0.05). At baseline, 5% carbon dioxide evoked a 16 ± 1% increase in cerebrovenous oxygen saturation, indicating vasodilatation. At 210 minutes, this response was nearly absent in SAL (4 ± 4%) (p < 0.05 vs. baseline) and Hb1 (1 ± 5%), but was partially preserved in Hb2 (9 ± 5%). There was no intergroup difference in beta amyloid precursor protein positive axons. Five of 20 SAL and 0 of 13 DCLHb animals developed brain death (flat electroencephalogram) (p = 0.05, SAL vs. DCLhb). Postresuscitation, DCLHb animals maintained higher mean pulmonary arterial pressure (28 ± 1 mm Hg, SAL; 42 ± mm Hg, Hb1; 45 ± 1 mm Hg, Hb2) (p < 0.05, Hb1 and Hb2 vs. SAL) and lower cardiac output (3.9 ± 1.6 L/min, SAL; 2.6 ± 0.1 L/min, Hb1; 2.7 ± 0.1 L/min, Hb2) (p < 0.05, Hb1 and Hb2 vs. SAL). Three Hb2 animals died as a result of cardiac failure, and one SAL animal died as a result of irreversible shock. Conclusion: In this swine model of traumatic brain injury and hemorrhagic shock, resuscitation with DCLHb maintained a higher cerebral perfusion pressure. Low-dose DCLHb (minimal increase in oxygen carriage) failed to significantly improve short-term outcome. With high-dose DCLHb (significant improvement in oxygen carriage), intracranial pressure was lower and cerebrovascular carbon dioxide reactivity was partially preserved; however, this was at the cost of poorer cardiac performance secondary to high afterload.

No description available.

Ischemic brain injury represents a major cause of death worldwide with limited treatment options with a narrow therapeutic window. Accordingly, novel treatments that extend the treatment from the early neuroprotective stage to the late regenerative phase may accommodate a much larger number of stroke patients. To this end, stem cell-based regenerative therapies may address this unmet clinical need. Several stem cell therapies have been tested as potentially exhibiting the capacity to regenerate the stroke brain. Based on the long track record and safety profile of transplantable stem cells for hematologic diseases, bone marrow-derived mesenchymal stromal cells or mesenchymal stromal cells have been widely tested in stroke animal models and have reached clinical trials. However, despite the translational promise of MSCs, probing cell function remains to be fully elucidated. Recognizing the multi-pronged cell death and survival processes that accompany stroke, here we review the literature on MSC definition, characterization, and mechanism of action in an effort to gain a better understanding towards optimizing its applications and functional outcomes in stroke. / National Institutes of Health / Revisión por pares

Introduction: Traumatic Brain Injury (TBI) remains a significant public health burden in the United States. Persons afflicted with more severe TBIs are usually admitted to an ICU, where they are at risk for a number of complications throughout their hospitalization. Recent literature has attempted to describe such complications from a cardiovascular perspective as part of a “cardio-cerebral syndrome.” We described the frequency of cardiac complications in the ICU among patients with a TBI and compared patients with and without measured cardiac dysfunction. We investigated the potential impact of cardiac dysfunction on in-hospital mortality. Methods: This was a retrospective review of a prospective cohort study in adult ICU patients with moderate-to-severe TBI (GCS≤12). We measured cardiac dysfunction using initial EKG echocardiography findings and peak serum troponin levels during hospitalization. Primary outcome was in-hospital mortality for patients with and without cardiac dysfunction using multivariable adjusted Cox Proportional Hazards Regression. Secondary outcomes examined the relationship between severity of brain injury and degree of cardiac dysfunction. Results: Ordinal logistic regression showed patients with more indicators of cardiac injury were significantly more likely to have greater brain injury as reflected by lower GCS scores (OR 0.76; 95%CI 0.58-0.99). There was a significantly increased multivariable adjusted risk of dying for each increase in measured cardiac injury (HR 2.41; 95% CI 1.29-4.53). Conclusions: Cardiac dysfunction was frequently observed in patients with TBI and we showed an association between increasing TBI severity and development of cardiac injury. Cardiovascular dysfunction was associated with an increased risk of in-hospital death. Adverse outcomes from TBI could potentially be mediated by cardiac injury, which could be used as a target for therapeutic intervention.

Includes bibliographical references / South Africa has a high incidence of injury-related disorders, such as traumatic brain injury (TBI) as a result of motor vehicle accidents and assault. Dysphagia is a common sequela of TBI, which may result in malnutrition or aspiration pneumonia. There is limited epidemiological data available for TBI and dysphagia in South Africa which is important for health care planning. There is also inadequate literature reporting predictive factors for dysphagia and health outcomes of patients with TBI and swallowing disorders for the South African context, which would provide management guidelines for Speech-Language Pathologists (SLPs) for patients with TBI and dysphagia. This study aims to begin to provide up-to-date information regarding the incidence of TBI and the prevalence of dysphagia in the population with TBI in Bloemfontein, South Africa. Predictive factors for dysphagia and health outcomes were also investigated in order to provide management guidelines for TBI-related dysphagia for SLPs. A prospective cohort study followed 77 participants aged 18 to 68 years (M = 33.1) with mild to severe traumatic brain injury, admitted to 2 state and 2 private hospitals in the Bloemfontein metropole, South Africa, to investigate the incidence of TBI and the prevalence of TBI-related dysphagia in the adult population in 2013. Participants were tracked from admission to hospital to discharge. Demographic and medical data was collected for each participant, including: gender, age, TBI aetiology, means of nutritional intake, respiratory status, length of hospital stay, and number of speech therapy sessions. Glasgow Coma Scale (GCS) scores at time of admission, swallowing evaluation, and discharge were noted as an indicator of TBI severity and each participant was assessed with the Mann Assessment of Swallowing Ability on admission and prior to discharge to assess the presence of dysphagia. The incidence of TBI for the Bloemfontein metropole was 353 per 100,000 people and was greater in the male than in the female population (11.83:1). The main mechanism for TBI in Bloemfontein was interpersonal violence (67.53%), followed by road traffic accidents (motor and pedestrian vehicle accidents; 23.38%). The prevalence rate for dysphagia was 32%. Twenty-eight percent of those who presented with dysphagia also aspirated. Severe TBI (GCS ≤ 8) was identified as a predictive factor for dysphagia. Participants with dysphagia had longer hospital stays (days; M = 22.04, SD = 17.67) than those with normal swallowing (M = 6.23, SD = 4.28), t(75) = 6.13, p < .001, and took significantly more days to achieve oral intake (M = 6.23, SD = 10.32) than those without dysphagia (M = .31, SD = 1.41), t(75) = 4.08, p < .001. Ventilation was associated with longer hospital stays, rs(25) = -.47, p = .02 and longer duration until achievement of oral intake, rs(22) = -.80, p < .001. Tracheotomised participants also had significantly longer hospital stays, rs(25) = -.67, p < .001, and took longer to achieve oral intake, rs(22) = -.52, p = .01. An increased period of time with a tracheostomy was also significantly associated with mortality, χ2(2, n = 11) = 6.52, p = .04. Participants with dysphagia (M = 3.84, SD = 5.44) required significantly more therapy sessions with an SLP than those without dysphagia (M = .15, SD = .64), t(75) = 4.85, p < .001, and those with low GCS scores were significantly less likely to achieve oral intake prior to discharge, rs(25) = -.45, p = .02, and had longer hospital stays than participants with mild head injuries, rs(25) = -.49, p = .01. All participants who received nutrition via nasogastric tubes returned to oral intake; however, individuals who had percutaneous endoscopic gastrostomies did not achieve oral intake prior to discharge. It is recommended that objective swallowing evaluations be conducted for patients admitted with severe TBIs, and patients with mild and moderate TBIs be screened to determine the presence of dysphagia. TBI prevention initiatives should be developed to reduce the incidence of TBI, specifically in the young adult male population.

Blast-related mild traumatic brain injury (mTBI) is a common injury among Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans due to the frequent use of improvised explosive devices (IEDs). A significant minority of veterans with blast-related mTBI complain of postconcussion symptoms (PCS) and cognitive difficulties, even years after the injury. Studies have suggested that these behavioral sequelae are primarily linked to mental health disorders such as posttraumatic stress disorder (PTSD). However, mTBI is associated with neural changes and the impact of these changes on behavioral sequelae is unclear. As such, this dissertation had three goals. First, this dissertation assessed whether the severity of PCS in blast-exposed individuals is associated with the extent of mTBI-related neural injury. Results revealed that individuals with mTBI with loss of consciousness (LOC) had significantly more white matter abnormalities than no-TBI controls and that these white matter abnormalities were spatially variable across individuals. Importantly, the extent of white matter abnormality was associated with physical PCS severity and mediated the relationship between mTBI with LOC and physical PCS. Second, this dissertation examined whether these white matter abnormalities were also associated with overall cognitive impairment. In light of the observed variability in white matter injury, a measure of overall cognitive status that takes into account heterogeneity of cognitive impairment was used. Results showed that the extent of white matter abnormality was associated with cognitive status and mediated the relationship between mTBI with LOC and cognitive impairment. Third, this dissertation examined performance and brain function in the context of an experimental measure of cognitive control known to be sensitive to residual effects of mTBI. Results revealed that although behavioral performance was similar across groups, the mTBI group had enhanced functional connectivity between brain networks important for task performance, suggesting a potential compensatory mechanism in mTBI. Together, the findings of this dissertation suggest that mTBI is associated with structural and functional connectivity alterations years after the injury. Further, this dissertation suggests that whereas structural connectivity changes may have negative behavioral consequences, changes in functional connectivity may serve as a compensatory mechanism for successful performance.