Articles: traumatic-brain-injuries.
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Malignant hyperthermia increases mortality and disability in patients with brain trauma. A clinical treatment for malignant hyperthermia following severe traumatic brain injury, termed 'cool and quiet' therapy by the authors of the current study, was investigated. Between June 2003 and June 2013, 110 consecutive patients with malignant hyperthermia following severe traumatic brain injury were treated using mild hypothermia (35-36°C) associated with small doses of sedative and muscle relaxant. ⋯ The therapy using mild hypothermia with a combination of sedative and muscle relaxant was beneficial in decreasing the mortality of patients with malignant hyperthermia following severe traumatic brain injury, particularly in patients with a GCS score within the range 3-5 on admission. The therapy was found to be safe, effective and convenient. However, rigorous clinical trials are required to provide evidence of the effectiveness of 'cool and quiet' therapy for hyperthermia.
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J Tissue Eng Regen Med · Feb 2015
Treatment of penetrating brain injury in a rat model using collagen scaffolds incorporating soluble Nogo receptor.
Injuries and diseases of the central nervous system (CNS) have the potential to cause permanent loss of brain parenchyma, with severe neurological consequences. Cavitary defects in the brain may afford the possibility of treatment with biomaterials that fill the lesion site while delivering therapeutic agents. This study examined the treatment of penetrating brain injury (PBI) in a rat model with collagen biomaterials and a soluble Nogo receptor (sNgR) molecule. sNgR was aimed at neutralizing myelin proteins that hinder axon regeneration by inducing growth cone collapse. ⋯ Immunohistochemical staining demonstrated the composition of the cellular infiltrate to include macrophages, astrocytes and vascular endothelial cells. Isolated regions of the scaffold borders showed integration with surrounding viable brain tissue that included neurons and oligodendrocytes. While axon regeneration was not detected in the scaffolds, the cellular infiltration and vascularization of the lesion site demonstrated a modification of the injury environment with implications for regenerative strategies.
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Experimental neurology · Feb 2015
Nrf2-ARE activator carnosic acid decreases mitochondrial dysfunction, oxidative damage and neuronal cytoskeletal degradation following traumatic brain injury in mice.
The importance of free radical-induced oxidative damage after traumatic brain injury (TBI) has been well documented. Despite multiple clinical trials with radical-scavenging antioxidants that are neuroprotective in TBI models, none is approved for acute TBI patients. As an alternative antioxidant target, Nrf2 is a transcription factor that activates expression of antioxidant and cytoprotective genes by binding to antioxidant response elements (AREs) within DNA. ⋯ This was accompanied by decreased oxidative damage to mitochondrial proteins, suggesting the mechanistic connection of the two effects. Lastly, delaying the initial administration of CA up to 8h post-TBI was still capable of reducing cytoskeletal breakdown, thereby demonstrating a clinically relevant therapeutic window for this approach. This study demonstrates that pharmacological Nrf2-ARE induction is capable of neuroprotective efficacy when administered after TBI.
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The 70-kDa heat shock protein (HSP70) is known to protect the brain from injury through multiple mechanisms. We investigated the effect of pharmacological HSP70 induction in experimental traumatic brain injury (TBI). 3-month-old male C57/B6 mice were given 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) intraperitoneally (IP, 2 mg/kg) or intracerebroventricularly (ICV, 1 μg/kg) to determine whether HSP70 could be induced in the brain. Mice were subjected to TBI via cortical controlled impact, and were treated with 17-AAG (or vehicle) IP according to one of two treatment regimens: (1) 2 mg/kg at the time of injury, (2) a total of three doses (4 mg/kg) at 2 and 1d prior to TBI and again at the time of injury. ⋯ Immunohistochemistry showed that both IP and ICV administration of 17-AAG increased HSP70 expression primarily in microglia and in a few neurons by 24 h but not in astrocytes. 17-AAG induced HSP70 in injured brain tissue as early as 6 h, peaking at 48 h and largely subsiding by 72 h after IP injection. Both treatment groups showed decreased hemorrhage volume relative to untreated mice as well as improved neurobehavioral outcomes. These observations indicate that pharmacologic HSP70 induction may prove to be a promising treatment for TBI.