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Papers by Avery Thomson
Expert review of neurotherapeutics, Jan 15, 2016
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor n... more Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron degeneration in the brain and spinal cord. Treatment development for ALS is complicated by complex underlying disease factors. Numerous tested drug compounds have shown no benefits in ALS patients, although effective in animal models. Discrepant results of pre-clinical animal studies and clinical trials for ALS have primarily been attributed to limitations of ALS animal models for drug-screening studies and methodological inconsistencies in human trials. Current status of pre-clinical and clinical trials in ALS is summarized. Specific blood-CNS barrier damage in ALS patients, as a novel potential reason for the clinical failures in drug therapies, is discussed. Expert commentary: Pathological perivascular collagen IV accumulation, one unique characteristic of barrier damage in ALS patients, could be hindering transport of therapeutics to the CNS. Restoration of B-CNS-B integrity wo...
Journal of Neuropathology & Experimental Neurology, 2016
We previously demonstrated blood-brain barrier impairment in remote contralateral brain areas in ... more We previously demonstrated blood-brain barrier impairment in remote contralateral brain areas in rats at 7 and 30 days after transient middle cerebral artery occlusion (tMCAO), indicating ischemic diaschisis. Here, we focused on effects of subacute and chronic focal cerebral ischemia on the blood-spinal cord barrier (BSCB). We observed BSCB damage on both sides of the cervical spinal cord in rats at 7 and 30 days post-tMCAO. Major BSCB ultrastructural changes in spinal cord gray and white matter included vacuolated endothelial cells containing autophagosomes, pericyte degeneration with enlarged mitochondria, astrocyte end-feet degeneration and perivascular edema; damaged motor neurons, swollen axons with unraveled myelin in ascending and descending tracts and astrogliosis were also observed. Evans Blue dye extravasation was maximal at 7 days. There was immunofluorescence evidence of reduction of microvascular expression of tight junction occludin, upregulation of Beclin-1 and LC3B immunoreactivities at 7 days and a reduction of the latter at 30 days post-ischemia. These novel pathological alterations on the cervical spinal cord microvasculature in rats after tMCAO suggest pervasive and long-lasting BSCB damage after focal cerebral ischemia, and that spinal cord ischemic diaschisis should be considered in the pathophysiology and therapeutic approaches in patients with ischemic cerebral infarction.
Expert review of neurotherapeutics, Jan 15, 2016
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor n... more Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron degeneration in the brain and spinal cord. Treatment development for ALS is complicated by complex underlying disease factors. Numerous tested drug compounds have shown no benefits in ALS patients, although effective in animal models. Discrepant results of pre-clinical animal studies and clinical trials for ALS have primarily been attributed to limitations of ALS animal models for drug-screening studies and methodological inconsistencies in human trials. Current status of pre-clinical and clinical trials in ALS is summarized. Specific blood-CNS barrier damage in ALS patients, as a novel potential reason for the clinical failures in drug therapies, is discussed. Expert commentary: Pathological perivascular collagen IV accumulation, one unique characteristic of barrier damage in ALS patients, could be hindering transport of therapeutics to the CNS. Restoration of B-CNS-B integrity wo...
Journal of Neuropathology & Experimental Neurology, 2016
We previously demonstrated blood-brain barrier impairment in remote contralateral brain areas in ... more We previously demonstrated blood-brain barrier impairment in remote contralateral brain areas in rats at 7 and 30 days after transient middle cerebral artery occlusion (tMCAO), indicating ischemic diaschisis. Here, we focused on effects of subacute and chronic focal cerebral ischemia on the blood-spinal cord barrier (BSCB). We observed BSCB damage on both sides of the cervical spinal cord in rats at 7 and 30 days post-tMCAO. Major BSCB ultrastructural changes in spinal cord gray and white matter included vacuolated endothelial cells containing autophagosomes, pericyte degeneration with enlarged mitochondria, astrocyte end-feet degeneration and perivascular edema; damaged motor neurons, swollen axons with unraveled myelin in ascending and descending tracts and astrogliosis were also observed. Evans Blue dye extravasation was maximal at 7 days. There was immunofluorescence evidence of reduction of microvascular expression of tight junction occludin, upregulation of Beclin-1 and LC3B immunoreactivities at 7 days and a reduction of the latter at 30 days post-ischemia. These novel pathological alterations on the cervical spinal cord microvasculature in rats after tMCAO suggest pervasive and long-lasting BSCB damage after focal cerebral ischemia, and that spinal cord ischemic diaschisis should be considered in the pathophysiology and therapeutic approaches in patients with ischemic cerebral infarction.