Experimental neurology
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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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Ischemic stroke is a major cause of death and long-term disability worldwide. Thrombolysis with recombinant tissue plasminogen activator is the only proven and effective treatment for acute ischemic stroke; however, therapeutic hypothermia is increasingly recognized as having a tissue-protective function and positively influencing neurological outcome, especially in cases of ischemia caused by cardiac arrest or hypoxic-ischemic encephalopathy in newborns. ⋯ This review discusses the mechanisms underlying the effect of hypothermia, as well as trends in hypothermia induction methods, methods for achieving optimal protection, side effects, and therapeutic strategies combining hypothermia with other neuroprotective treatments. Finally, outstanding issues that must be addressed before hypothermia treatment is implemented at a clinical level are also presented.
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Experimental neurology · Oct 2015
ReviewNeurodevelopmental implications of the general anesthesia in neonate and infants.
Each year, about six million children, including 1.5 million infants, in the United States undergo surgery with general anesthesia, often requiring repeated exposures. However, a crucial question remains of whether neonatal anesthetics are safe for the developing central nervous system (CNS). General anesthesia encompasses the administration of agents that induce analgesic, sedative, and muscle relaxant effects. ⋯ While the casual relationship between cellular toxicity and neurological impairments is still not clear, recent reports in animal experiments showed that anesthetics in neonates can affect neurogenesis, which could be a possible mechanism underlying the chronic effect of anesthetics. Understanding the cellular and molecular mechanisms of anesthetic effects will help to define the scope of the problem in humans and may lead to preventive and therapeutic strategies. Therefore, in this review, we summarize the current evidence on neonatal anesthetic effects in the developmental CNS and discuss how factors influencing these processes can be translated into new therapeutic strategies.
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Experimental neurology · Oct 2015
Review Case ReportsVenous system in acute brain injury: Mechanisms of pathophysiological change and function.
Cerebral vascular injury is a major component of acute brain injury. Currently, neuroprotective strategies primarily focus on the recanalization of cerebral arteries and capillaries, and the protection of insulted neurons. ⋯ Recent progress in the neurobiological understanding of the vascular neural network has demonstrated that cerebral venous systems are able to respond to acute brain injury by regulating the blood flow disharmony following brain edema, blood brain barrier disruption, ischemia, and hemorrhage. With the evidence presented in this review, future clinical management of acutely brain injured patients will expand to include the recirculation concept, establishing a harmony between arterial and venous systems, in addition to the established recanalization and reperfusion strategies.
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Experimental neurology · Jul 2015
ReviewChondroitin sulfate proteoglycans: Key modulators in the developing and pathologic central nervous system.
Chondroitin Sulfate Proteoglycans (CSPGs) are a major component of the extracellular matrix in the central nervous system (CNS) and play critical role in the development and pathophysiology of the brain and spinal cord. Developmentally, CSPGs provide guidance cues for growth cones and contribute to the formation of neuronal boundaries in the developing CNS. Their presence in perineuronal nets plays a crucial role in the maturation of synapses and closure of critical periods by limiting synaptic plasticity. ⋯ Moreover, the recent discovery of multiple receptors for CSPGs provides new therapeutic targets for targeted interventions in blocking the inhibitory properties of CSPGs following injury. Here, we will provide an in depth discussion on the impact of CSPGs in normal and pathological CNS. We will also review the recent preclinical therapies that have been developed to target CSPGs in the injured CNS.