Blood-brain barrier disruption results in delayed functional and structural alterations in the rat neocortex.
Disruption of the blood-brain barrier (BBB) is a characteristic finding in common neurological disorders. Human data suggest BBB disruption may underlie cerebral dysfunction. Animal experiments show the development of epileptiform activity following BBB breakdown. In the present study we investigated the neurophysiological, structural and functional consequences of BBB disruption. Adult rats underwent focal BBB disruption in the rat sensory-motor cortex using the bile salt sodium deoxycholate (DOC). Magnetic resonance imaging in-vivo showed an early BBB disruption with delayed reduction in cortical volume. This was associated with a reduced number of neurons and an increased number of astrocytes. In-vitro experiments showed that the threshold for spreading depression and the propagation velocity of the evoked epileptic potentials were increased 1 month after treatment. Furthermore, animals' motor functions deteriorated during the first few weeks following BBB disruption. Treatment with serum albumin resulted in a similar cell loss confirming that the effect of DOC was due to opening of the BBB. Our findings suggest that delayed neurodegeneration and functional impairment occur following the development of the epileptic focus in the BBB-permeable cerebral cortex.
Tomkins
O
O
Department of Physiology, Soroka Medical Center and Zlotowski Center for Neuroscience, Ben-Gurion University, Beer-Sheva, Israel.
Friedman
O
O
Ivens
S
S
Reiffurth
C
C
Major
S
S
Dreier
J P
JP
Heinemann
U
U
Friedman
A
A
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D001284:Atrophy / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D002536:Cerebral Arteries / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D013181:Cortical Spreading Depression / Q000187:drug effects / Q000502:physiology; D003840:Deoxycholic Acid / Q000009:adverse effects; D004409:Dyskinesia, Drug-Induced / Q000473:pathology / Q000503:physiopathology; D004827:Epilepsy / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D005911:Gliosis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D019579:Neocortex / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000009:adverse effects; D013997:Time Factors
D012709:Serum Albumin; D003840:Deoxycholic Acid