Blood-Spinal Cord Barrier Alterations in Subacute and Chronic Stages of a Rat Model of Focal Cerebral Ischemia.
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.
From the Center of Excellence for Aging & Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, NT, AT, JB, SNW, EDH, HQ, AF-D, JVA, PRS, CVB); Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, PRS, HVL, CVB); Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D); Department of Pathology and Cell Biology, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, PRS); Department of Integrative Biology, University of South Florida, Tampa, Florida (EH); Department of Psychiatry, Morsani College of Medicine, University of South Florida, Tampa, Florida (PRS). sgarbuzo@health.usf.edu.
Svitlana
S
Garbuzova-Davis
From the Center of Excellence for Aging & Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, NT, AT, JB, SNW, EDH, HQ, AF-D, JVA, PRS, CVB); Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, PRS, HVL, CVB); Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D); Department of Pathology and Cell Biology, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, PRS); Department of Integrative Biology, University of South Florida, Tampa, Florida (EH); Department of Psychiatry, Morsani College of Medicine, University of South Florida, Tampa, Florida (PRS).
Edward
E
Haller
From the Center of Excellence for Aging & Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, NT, AT, JB, SNW, EDH, HQ, AF-D, JVA, PRS, CVB); Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, PRS, HVL, CVB); Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D); Department of Pathology and Cell Biology, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, PRS); Department of Integrative Biology, University of South Florida, Tampa, Florida (EH); Department of Psychiatry, Morsani College of Medicine, University of South Florida, Tampa, Florida (PRS).
Naoki
N
Tajiri
From the Center of Excellence for Aging & Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, NT, AT, JB, SNW, EDH, HQ, AF-D, JVA, PRS, CVB); Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, PRS, HVL, CVB); Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D); Department of Pathology and Cell Biology, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, PRS); Department of Integrative Biology, University of South Florida, Tampa, Florida (EH); Department of Psychiatry, Morsani College of Medicine, University of South Florida, Tampa, Florida (PRS).
Avery
A
Thomson
From the Center of Excellence for Aging & Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, NT, AT, JB, SNW, EDH, HQ, AF-D, JVA, PRS, CVB); Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, PRS, HVL, CVB); Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D); Department of Pathology and Cell Biology, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, PRS); Department of Integrative Biology, University of South Florida, Tampa, Florida (EH); Department of Psychiatry, Morsani College of Medicine, University of South Florida, Tampa, Florida (PRS).
Jennifer
J
Barretta
From the Center of Excellence for Aging & Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, NT, AT, JB, SNW, EDH, HQ, AF-D, JVA, PRS, CVB); Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, PRS, HVL, CVB); Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D); Department of Pathology and Cell Biology, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, PRS); Department of Integrative Biology, University of South Florida, Tampa, Florida (EH); Department of Psychiatry, Morsani College of Medicine, University of South Florida, Tampa, Florida (PRS).
Stephanie N
SN
Williams
From the Center of Excellence for Aging & Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, NT, AT, JB, SNW, EDH, HQ, AF-D, JVA, PRS, CVB); Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, PRS, HVL, CVB); Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D); Department of Pathology and Cell Biology, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, PRS); Department of Integrative Biology, University of South Florida, Tampa, Florida (EH); Department of Psychiatry, Morsani College of Medicine, University of South Florida, Tampa, Florida (PRS).
Eithan D
ED
Haim
From the Center of Excellence for Aging & Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, NT, AT, JB, SNW, EDH, HQ, AF-D, JVA, PRS, CVB); Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, PRS, HVL, CVB); Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D); Department of Pathology and Cell Biology, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, PRS); Department of Integrative Biology, University of South Florida, Tampa, Florida (EH); Department of Psychiatry, Morsani College of Medicine, University of South Florida, Tampa, Florida (PRS).
Hua
H
Qin
From the Center of Excellence for Aging & Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, NT, AT, JB, SNW, EDH, HQ, AF-D, JVA, PRS, CVB); Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, PRS, HVL, CVB); Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D); Department of Pathology and Cell Biology, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, PRS); Department of Integrative Biology, University of South Florida, Tampa, Florida (EH); Department of Psychiatry, Morsani College of Medicine, University of South Florida, Tampa, Florida (PRS).
Aric
A
Frisina-Deyo
From the Center of Excellence for Aging & Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, NT, AT, JB, SNW, EDH, HQ, AF-D, JVA, PRS, CVB); Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, PRS, HVL, CVB); Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D); Department of Pathology and Cell Biology, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, PRS); Department of Integrative Biology, University of South Florida, Tampa, Florida (EH); Department of Psychiatry, Morsani College of Medicine, University of South Florida, Tampa, Florida (PRS).
Jerry V
JV
Abraham
From the Center of Excellence for Aging & Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, NT, AT, JB, SNW, EDH, HQ, AF-D, JVA, PRS, CVB); Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, PRS, HVL, CVB); Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D); Department of Pathology and Cell Biology, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, PRS); Department of Integrative Biology, University of South Florida, Tampa, Florida (EH); Department of Psychiatry, Morsani College of Medicine, University of South Florida, Tampa, Florida (PRS).
Paul R
PR
Sanberg
From the Center of Excellence for Aging & Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, NT, AT, JB, SNW, EDH, HQ, AF-D, JVA, PRS, CVB); Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, PRS, HVL, CVB); Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D); Department of Pathology and Cell Biology, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, PRS); Department of Integrative Biology, University of South Florida, Tampa, Florida (EH); Department of Psychiatry, Morsani College of Medicine, University of South Florida, Tampa, Florida (PRS).
Harry
H
Van Loveren
From the Center of Excellence for Aging & Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, NT, AT, JB, SNW, EDH, HQ, AF-D, JVA, PRS, CVB); Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, PRS, HVL, CVB); Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D); Department of Pathology and Cell Biology, Morsani College of Medicine, University of South Florida, Tampa, Florida (SG-D, PRS); Department of Integrative Biology, University of South Florida, Tampa, Florida (EH); Department of Psychiatry, Morsani College of Medicine, University of South Florida, Tampa, Florida (PRS).
Cesario V
CV
Borlongan
D000208:Acute Disease; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology*; D002908:Chronic Disease; D004195:Disease Models, Animal; D008297:Male; D055806:Microvessels / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure
Astrocytes; Autophagosomes; Blood-spinal cord barrier (BSCB); Middle cerebral artery occlusion (MCAO); Stroke; Subacute and chronic diaschisis; Tract demyelination.