Traumatic brain injury remains a global health crisis that spans all demographics,yet there exist limited treatment options that may effectively curtail its lingering symptoms.Traumatic brain injury pathology entails ...Traumatic brain injury remains a global health crisis that spans all demographics,yet there exist limited treatment options that may effectively curtail its lingering symptoms.Traumatic brain injury pathology entails a progression from primary injury to inflammation-mediated secondary cell death.Sequestering this inflammation as a means of ameliorating the greater symptomology of traumatic brain injury has emerged as an attractive treatment prospect.In this review,we recapitulate and evaluate the important developments relating to regulating traumatic brain injury-induced neuroinflammation,edema,and blood-brain barrier disintegration through pharmacotherapy and stem cell transplants.Although these studies of stand-alone treatments have yielded some positive results,more therapeutic outcomes have been documented from the promising area of combined drug and stem cell therapy.Harnessing the facilitatory properties of certain pharmaceuticals with the anti-inflammatory and regenerative effects of stem cell transplants creates a synergistic effect greater than the sum of its parts.The burgeoning evidence in favor of combined drug and stem cell therapies warrants more elaborate preclinical studies on this topic in order to pave the way for later clinical trials.展开更多
Stroke persists as a global health and economic crisis,yet only two interventions to reduce stroke-induced brain injury exist.In the clinic,many patients who experience an ischemic stroke often further suffer from ret...Stroke persists as a global health and economic crisis,yet only two interventions to reduce stroke-induced brain injury exist.In the clinic,many patients who experience an ischemic stroke often further suffer from retinal ischemia,which can inhibit their ability to make a functional recovery and may diminish their overall quality of life.Despite this,no treatments for retinal ischemia have been developed.In both cases,ischemia-induced mitochondrial dysfunction initiates a cell loss cascade and inhibits endogenous brain repair.Stem cells have the ability to transfer healthy and functional mitochondria not only ischemic neurons,but also to similarly endangered retinal cells,replacing their defective mitochondria and thereby reducing cell death.In this review,we encapsulate and assess the relationship between cerebral and retinal ischemia,recent preclinical advancements made using in vitro and in vivo retinal ischemia models,the role of mitochondrial dysfunction in retinal ischemia pathology,and the therapeutic potential of stem cell-mediated mitochondrial transfer.Furthermore,we discuss the pitfalls in classic rodent functional assessments and the potential advantages of laser Doppler as a metric of stroke progression.The studies evaluated in this review highlight stem cell-derived mitochondrial transfer as a novel therapeutic approach to both retinal ischemia and stroke.Furthermore,we posit the immense correlation between cerebral and retinal ischemia as an underserved area of study,warranting exploration with the aim of these treating injuries together.展开更多
基金CVB was funded by National Institutes of Health(NIH)R01NS071956,NIH R01NS090962,NIH R21NS089851,NIH R21NS094087Veterans Affairs Merit Review I01 BX001407
文摘Traumatic brain injury remains a global health crisis that spans all demographics,yet there exist limited treatment options that may effectively curtail its lingering symptoms.Traumatic brain injury pathology entails a progression from primary injury to inflammation-mediated secondary cell death.Sequestering this inflammation as a means of ameliorating the greater symptomology of traumatic brain injury has emerged as an attractive treatment prospect.In this review,we recapitulate and evaluate the important developments relating to regulating traumatic brain injury-induced neuroinflammation,edema,and blood-brain barrier disintegration through pharmacotherapy and stem cell transplants.Although these studies of stand-alone treatments have yielded some positive results,more therapeutic outcomes have been documented from the promising area of combined drug and stem cell therapy.Harnessing the facilitatory properties of certain pharmaceuticals with the anti-inflammatory and regenerative effects of stem cell transplants creates a synergistic effect greater than the sum of its parts.The burgeoning evidence in favor of combined drug and stem cell therapies warrants more elaborate preclinical studies on this topic in order to pave the way for later clinical trials.
基金funded by the National Institutes of Health(NIH)R01NS071956,NIH R01NS090962,NIH R21NS089851,NIH R21NS094087Veterans Affairs Merit Review I01 BX001407(all to CVB)
文摘Stroke persists as a global health and economic crisis,yet only two interventions to reduce stroke-induced brain injury exist.In the clinic,many patients who experience an ischemic stroke often further suffer from retinal ischemia,which can inhibit their ability to make a functional recovery and may diminish their overall quality of life.Despite this,no treatments for retinal ischemia have been developed.In both cases,ischemia-induced mitochondrial dysfunction initiates a cell loss cascade and inhibits endogenous brain repair.Stem cells have the ability to transfer healthy and functional mitochondria not only ischemic neurons,but also to similarly endangered retinal cells,replacing their defective mitochondria and thereby reducing cell death.In this review,we encapsulate and assess the relationship between cerebral and retinal ischemia,recent preclinical advancements made using in vitro and in vivo retinal ischemia models,the role of mitochondrial dysfunction in retinal ischemia pathology,and the therapeutic potential of stem cell-mediated mitochondrial transfer.Furthermore,we discuss the pitfalls in classic rodent functional assessments and the potential advantages of laser Doppler as a metric of stroke progression.The studies evaluated in this review highlight stem cell-derived mitochondrial transfer as a novel therapeutic approach to both retinal ischemia and stroke.Furthermore,we posit the immense correlation between cerebral and retinal ischemia as an underserved area of study,warranting exploration with the aim of these treating injuries together.
