title: Not just the brain: methamphetamine disrupts blood-spinal cord barrier and induces acute glial activation and structural damage of spinal cord cells.
abstract: Acute methamphetamine (METH) intoxication induces metabolic brain activation as well as multiple physiological and behavioral responses that could result in life-threatening health complications. Previously, we showed that METH (9 mg/kg) used in freely moving rats induces robust leakage of blood-brain barrier, acute glial activation, vasogenic edema, and structural abnormalities of brain cells. These changes were tightly correlated with drug-induced brain hyperthermia and were greatly potentiated when METH was used at warm ambient temperatures (29°C), inducing more robust and prolonged hyperthermia. Extending this line of research, here we show that METH also strongly increases the permeability of the blood-spinal cord barrier as evidenced by entry of Evans blue and albumin immunoreactivity in T9-12 segments of the spinal cord. Similar to the blood-brain barrier, leakage of bloodspinal cord barrier was associated with acute glial activation, alterations of ionic homeostasis, water tissue accumulation (edema), and structural abnormalities of spinal cord cells. Similar to that in the brain, all neurochemical alterations correlated tightly with drug-induced elevations in brain temperature and they were enhanced when the drug was used at 29°C and brain hyperthermia reached pathological levels (>40°C). We discuss common features and differences in neural responses between the brain and spinal cord, two inseparable parts of the central nervous system affected by METH exposure.
authors: Eugene A
authors: EA
authors: Kiyatkin
authors: Uppsala University, University Hospital, Anesthesiology & Intensive Care Medicine, Dept. Surgical Sciences; Frodingsgatan 12:28, SE-75421; Uppsala, Sweden. Sharma@surgsci.uu.se.
authors: Hari S
authors: HS
authors: Sharma
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000293:injuries / Q000648:ultrastructure; D001831:Body Temperature; D001921:Brain / Q000187:drug effects; D001929:Brain Edema / Q000139:chemically induced; D002199:Capillary Permeability / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D005334:Fever / Q000139:chemically induced*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D009457:Neuroglia / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D020318:Rats, Long-Evans; D013116:Spinal Cord / Q000473:pathology* / Q000648:ultrastructure
chemical_list: D000697:Central Nervous System Stimulants; D005904:Glial Fibrillary Acidic Protein; D008694:Methamphetamine