Experimental neurology
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Experimental neurology · Jun 2010
Effects of Aquaporin-4 on edema formation following intracerebral hemorrhage.
Intracerebral hemorrhage (ICH) constitutes 10% to 15% of all strokes and is associated with high morbidity and mortality. To date, little is known about the role of AQP4 (Aquaporin-4), which is abundantly expressed in pericapillary astrocyte foot processes and in edema formation after intracerebral hemorrhage. The purpose of this study was to examine the role of AQP4 in edema formation after ICH by using AQP4(-/-) mice. ⋯ These results suggest that AQP4 deletion increases ICH damage, including edema formation, blood-brain barrier damage and neuronal death/TUNEL-positive cells. Further studies on the protective role of activated AQP4 expression following ICH may provide useful therapeutic target for ICH-induced brain injury.
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Experimental neurology · May 2010
ReviewThe potentiation of peripheral nerve sheaths in regeneration and repair.
Traumatic injury to the nervous system often results in life changing loss of neurological function. Spontaneous neural regeneration occurs rarely and the outcome of therapeutic intervention is most often unacceptable. An intensive effort is underway to improve methods and technologies for nervous system repair. ⋯ Experimental alteration of nerve sheath composition can also potentiate nerve and improve key features of nerve regeneration. For instance, enzymatic degradation of inhibitory chondroitin sulfate proteoglycan mimics endogenous processes that potentiate degenerated nerve and improves the outcome of direct nerve repair and grafting in animal models. This review provides a perspective of the essential role that peripheral nerve sheaths play in regulating axonal regeneration and focuses on discoveries leading to the inception and development of novel therapies for nerve repair.
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Experimental neurology · May 2010
ReviewA conditioning lesion induces changes in gene expression and axonal transport that enhance regeneration by increasing the intrinsic growth state of axons.
Injury of axons in the peripheral nervous system (PNS) induces transcription-dependent changes in gene expression and axonal transport that promote effective regeneration by increasing the intrinsic growth state of axons. Regeneration is enhanced in axons re-injured 1-2 weeks after the intrinsic growth state has been increased by such a prior conditioning lesion (CL). The intrinsic growth state does not increase after axons are injured in the mammalian central nervous system (CNS), where they lack the capacity for effective regeneration. ⋯ A CL of peripheral branches increases the intrinsic growth state of central branches in the dorsal columns of the spinal cord, enabling these axons to undergo lengthy regeneration in a segment of peripheral nerve transplanted into the spinal cord (i.e., a peripheral nerve graft). This regeneration does not occur in the absence of a CL. We will examine how changes in gene expression and axonal transport induced by a CL may promote this regeneration.
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Experimental neurology · May 2010
Mesenchymal stem cell transplantation in amyotrophic lateral sclerosis: A Phase I clinical trial.
Amyotrophic Lateral Sclerosis (ALS) is a devastating incurable disease. Stem-cell-based therapies represent a new possible strategy for ALS clinical research. The objectives of this Phase 1 clinical study were to assess the feasibility and toxicity of mesenchymal stem cell transplantation and to test the impact of a cell therapy in ALS patients. ⋯ Magnetic resonance images (MRI) showed no structural changes (including tumor formation) in either the brain or the spinal cord. However the lack of post mortem material prevents any definitive conclusion about the vitality of the MSCs after transplantation. In conclusion, this study confirms that MSC transplantation into the spinal cord of ALS patients is safe and that MSCs might have a clinical use for future ALS cell based clinical trials.
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Experimental neurology · May 2010
A human neuron injury model for molecular studies of axonal regeneration.
The enhancement of regeneration of damaged axons in both the peripheral and central nervous systems is a widely pursued goal in clinical medicine. Although some of the molecular mechanisms involved in the intrinsic neurite regeneration program have been elucidated, much additional study is required for development of new therapeutics. The majority of studies in the field of axonal regeneration have utilized animal models due to obvious limitations of the accessibility of human neural tissues. ⋯ Profound changes in gene expression were observed over a time course of 2 to 24 hours after lesion. The expression of several genes reported to be involved in axonal injury responses in animal models changed following injury of hESC-derived neurons. Thus, hESC-derived neurons may be a useful in vitro model system for mechanistic studies on human axonal injury and regeneration.