Behavioral Deficits in Animal Models of Blast Traumatic Brain Injury

IntroductionThere is little systematic tracking or detailed analysis of investments in research and development for blast injury to support decision-making around research future funding.MethodsThis study examined global investments into blast injury-related research from public and philanthropic funders across 2000–2019. Research databases were searched using keywords, and open data were extracted from funder websites. Data collected included study title, abstract, award amount, funder and year. Individual awards were categorised to compare amounts invested into different blast injuries, the scientific approaches taken and analysis of research investment into blast traumatic brain injury (TBI).ResultsA total of 806 awards were identified into blast injury-related research globally, equating to US$902.1 million (m, £565.9m GBP). There was a general increase in year-on-year investment between 2003 and 2009 followed by a consistent decline in annual funding since 2010. Pre-clinical research received $671.3 m (74.4%) of investment. Brain-related injury research received $427.7 m (47.4%), orthopaedic injury $138.6 m (15.4%), eye injury $63.7 m (7.0%) and ear injury $60.5m (6.7%). Blast TBI research received a total investment of $384.3 m, representing 42.6% of all blast injury-related research. The U.S. Department of Defense funded $719.3 m (80%).ConclusionsInvestment data suggest that blast TBI research has received greater funding than other blast injury health areas. The funding pattern observed can be seen as reactive, driven by the response to the War on Terror, the rising profile of blast TBI and congressionally mandated research.

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3,6′-Dithiopomalidomide Ameliorates Hippocampal Neurodegeneration, Microgliosis and Astrogliosis and Improves Cognitive Behaviors in Rats with a Moderate Traumatic Brain Injury

International Journal of Molecular Sciences ◽

10.3390/ijms22158276 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8276

Author(s):

Pen-Sen Huang ◽

Ping-Yen Tsai ◽

Ling-Yu Yang ◽

Daniela Lecca ◽

Weiming Luo ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Short Term Memory ◽

Post Injury ◽

Behavioral Deficits ◽

Cognitive Behaviors ◽

Moderate Traumatic Brain Injury ◽

Short And Long Term ◽

Behavioral Impairments ◽

Hippocampal Neurodegeneration

Traumatic brain injury (TBI) is a leading cause of disability and mortality worldwide. It can instigate immediate cell death, followed by a time-dependent secondary injury that results from disproportionate microglial and astrocyte activation, excessive inflammation and oxidative stress in brain tissue, culminating in both short- and long-term cognitive dysfunction and behavioral deficits. Within the brain, the hippocampus is particularly vulnerable to a TBI. We studied a new pomalidomide (Pom) analog, namely, 3,6′-dithioPom (DP), and Pom as immunomodulatory imide drugs (IMiD) for mitigating TBI-induced hippocampal neurodegeneration, microgliosis, astrogliosis and behavioral impairments in a controlled cortical impact (CCI) model of TBI in rats. Both agents were administered as a single intravenous dose (0.5 mg/kg) at 5 h post injury so that the efficacies could be compared. Pom and DP significantly reduced the contusion volume evaluated at 24 h and 7 days post injury. Both agents ameliorated short-term memory deficits and anxiety behavior at 7 days after a TBI. The number of degenerating neurons in the CA1 and dentate gyrus (DG) regions of the hippocampus after a TBI was reduced by Pom and DP. DP, but not Pom, significantly attenuated the TBI-induced microgliosis and DP was more efficacious than Pom at attenuating the TBI-induced astrogliosis in CA1 and DG at 7D after a TBI. In summary, a single intravenous injection of Pom or DP, given 5 h post TBI, significantly reduced hippocampal neurodegeneration and prevented cognitive deficits with a concomitant attenuation of the neuroinflammation in the hippocampus.

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Intraoperative hypothermia during vascular neurosurgical procedures

Neurosurgical FOCUS ◽

10.3171/2009.3.focus0927 ◽

2009 ◽

Vol 26 (5) ◽

pp. E24 ◽

Cited By ~ 11

Author(s):

Raymond Choi ◽

Robert H. Andres ◽

Gary K. Steinberg ◽

Raphael Guzman

Keyword(s):

Traumatic Brain Injury ◽

Clinical Trials ◽

Brain Injury ◽

Animal Models ◽

Mild Hypothermia ◽

Scientific Evidence ◽

Neurosurgical Procedures ◽

Ischemic Damage ◽

Intraoperative Hypothermia ◽

Improved Outcomes

Increasing evidence in animal models and clinical trials for stroke, hypoxic encephalopathy for children, and traumatic brain injury have shown that mild hypothermia may attenuate ischemic damage and improve neurological outcome. However, it is less clear if mild intraoperative hypothermia during vascular neurosurgical procedures results in improved outcomes for patients. This review examines the scientific evidence behind hypothermia as a treatment and discusses factors that may be important for the use of this adjuvant technique, including cooling temperature, duration of hypothermia, and rate of rewarming.

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Sex-Specific Chronic Behavioral Deficits following Mild Traumatic Brain Injury in the Adolescent Rat

10.17918/58pp-z161 ◽

2021 ◽

Author(s):

Laura Giacometti

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Mild Traumatic Brain Injury ◽

Behavioral Deficits

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Severe Traumatic Brain Injury

10.2310/psych.2403 ◽

2018 ◽

Author(s):

Ryan Martin ◽

Lara Zimmermann ◽

Kee D. Kim ◽

Marike Zwienenberg ◽

Kiarash Shahlaie

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Intracranial Pressure ◽

Severe Traumatic Brain Injury ◽

Neurocritical Care ◽

Secondary Brain Injury ◽

Brain Oxygenation ◽

Barbiturate Coma ◽

Blast Traumatic Brain Injury ◽

Penetrating Traumatic Brain Injury

Traumatic brain injury remains a leading cause of death and disability worldwide. Patients with severe traumatic brain injury are best treated with a multidisciplinary, evidence-based, protocol-directed approach, which has been shown to decrease mortality and improve functional outcomes. Therapy is directed at the prevention of secondary brain injury through optimizing cerebral blood flow and the delivery of metabolic fuel (ie, oxygen and glucose). This is accomplished through the measurement and treatment of elevated intracranial pressure (ICP), the strict avoidance of hypotension and hypoxemia, and in some instances, surgical management. The treatment of elevated ICP is approached in a protocolized, tiered manner, with escalation of care occurring in the setting of refractory intracranial hypertension, culminating in either decompressive surgery or barbiturate coma. With such an approach, the rates of mortality secondary to traumatic brain injury are declining despite an increasing incidence of traumatic brain injury. This review contains 3 figures, 5 tables and 69 reference Key Words: blast traumatic brain injury, brain oxygenation, cerebral perfusion pressure, decompressive craniectomy, hyperosmolar therapy, intracranial pressure, neurocritical care, penetrating traumatic brain injury, severe traumatic brain injury

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