Experimental neurology
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Experimental neurology · Jan 2016
ReviewCurrent status of fluid biomarkers in mild traumatic brain injury.
Mild traumatic brain injury (mTBI) affects millions of people annually and is difficult to diagnose. Mild injury is insensitive to conventional imaging techniques and diagnoses are often made using subjective criteria such as self-reported symptoms. Many people who sustain a mTBI develop persistent post-concussive symptoms. ⋯ Most studies use a hypothesis-driven approach, screening biofluids for markers known to be associated with TBI pathophysiology. This approach has yielded limited success in identifying markers that can be used clinically, additional candidate biomarkers are needed. Innovative and unbiased methods such as proteomics, microRNA arrays, urinary screens, autoantibody identification and phage display would complement more traditional approaches to aid in the discovery of novel mTBI biomarkers.
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Traumatic brain injury (TBI) imparts a significant health burden in the United States, leaving many patients with chronic deficits. Improvement in clinical outcome following TBI has been hindered by a lack of treatments that have proven successful during phase III trials. Research remains active into a variety of non-pharmacologic, small molecule, endocrine and cell based therapies. ⋯ Increasingly, studies have shown that these cells are able to attenuate the inflammatory response to injury and stimulate production of neurotrophic factors. In animal models, beneficial effects on blood-brain barrier permeability, neuroprotection and neural repair through enhanced axonal remodeling have been observed. Clinical investigation with cell therapies for TBI remains ongoing.
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Experimental neurology · Jan 2016
Repetitive mild traumatic brain injury with impact acceleration in the mouse: Multifocal axonopathy, neuroinflammation, and neurodegeneration in the visual system.
Repetitive mild traumatic brain injury (mTBI) is implicated in chronic neurological illness. The development of animal models of repetitive mTBI in mice is essential for exploring mechanisms of these chronic diseases, including genetic vulnerability by using transgenic backgrounds. In this study, the rat model of impact acceleration (IA) was redesigned for the mouse cranium and used in two clinically relevant repetitive mTBI paradigms. ⋯ Our findings establish a new model of repetitive mTBI model featured by TAI in discrete CNS tracts, especially the visual system and cerebellum. Injury in retina and optic nerve provides a sensitive measure of severity of mTBI, thus enabling further studies on mechanisms and experimental therapeutics. Our model can also be useful in exploring mechanisms of chronic neurological disease caused by repetitive mTBI in wild-type and transgenic mice.
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Experimental neurology · Jan 2016
Brainstem node for loss of consciousness due to GABA(A) receptor-active anesthetics.
The molecular agents that induce loss of consciousness during anesthesia are classically believed to act by binding to cognate transmembrane receptors widely distributed in the CNS and critically suppressing local processing and network connectivity. However, previous work has shown that microinjection of anesthetics into a localized region of the brainstem mesopontine tegmentum (MPTA) rapidly and reversibly induces anesthesia in the absence of global spread. This implies that functional extinction is determined by neural pathways rather than vascular distribution of the anesthetic agent. ⋯ Combined with the prior microinjection data, we conclude that drug delivery to the MPTA is sufficient to induce loss-of-consciousness and that neurons in this locus are necessary for anesthetic induction at clinically relevant doses. Together, the results support an architecture for anesthesia with the MPTA serving as a key node in an endogenous network of dedicated pathways that switch between wake and unconsciousness. As such, the MPTA might also play a role in syncope, concussion and sleep.
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Experimental neurology · Nov 2015
Chronic stress and peripheral pain: Evidence for distinct, region-specific changes in visceral and somatosensory pain regulatory pathways.
Chronic stress alters the hypothalamic-pituitary-adrenal (HPA) axis and enhances visceral and somatosensory pain perception. It is unresolved whether chronic stress has distinct effects on visceral and somatosensory pain regulatory pathways. Previous studies reported that stress-induced visceral hyperalgesia is associated with reciprocal alterations of endovanilloid and endocannabinoid pain pathways in DRG neurons innervating the pelvic viscera. ⋯ Behavioral assessment showed that visceral hyperalgesia persisted, whereas somatosensory hyperalgesia and enhanced expression of Nav1.7 and Nav1.8 sodium channels in L4-L5 DRGs normalized 3 days after completion of the stress phase. These data indicate that chronic stress induces visceral and somatosensory hyperalgesia that involves differential changes in endovanilloid and endocannabinoid pathways, and sodium channels in DRGs innervating the pelvic viscera and lower extremities. These results suggest that chronic stress-induced visceral and lower extremity somatosensory hyperalgesia can be treated selectively at different levels of the spinal cord.