Treatment of brain trauma with liposomal superoxide dismutase.
Brain trauma was induced in rats by impact of a steel bar on the head with a force such that damage (as measured by neurological scoring) was reversible in fourteen days. Systemic treatment (intraperitoneal injections) with free bovine copper superoxide dismutase or a liposomal form of the enzyme considerably shortened recovery time to less than half. Tests included cranial nerves--cornean and aural reflexes, and sensorial motricity functions--gripping reflexes, displacement reactions, recovery and flexion reflexes, equilibrium tests and spontaneous mobility. Normalisation of EEG recordings was also greatly accelerated in the case of treated animals. No changes of brain glutathione peroxidase, glutathione transferase or Mn superoxide dismutase in traumatized animals were observed. However a slight decrease in Cu-SOD occurs. Cerebral lipoperoxidation is increased in the traumatized animals compared with controls. This increase is reduced on treatment of the rats with liposomal SOD (or the free enzyme). Very small amounts of the exogenous SOD pass the brain barrier, the permeability of which is increased in traumatized animals. The enzyme is particularly concentrated in the cortex. Despite apparent total neurological recovery at 15 days for untreated traumatized animals, significant differences in EEG recordings, in percentage cerebral water content and in histological examination of brain tissue of these controls compared with treated animals were observed with a net improvement in the latter case. The results obtained with this model suggest that clinical treatment of coma states and brain traumas with liposomal superoxide dismutase may have certain advantages over orthodox treatments.
Michelson
A M
AM
Institut de Biologie Physico-Chimique, Paris, France.
Jadot
G
G
Puget
K
K
D000818:Animals; D001921:Brain / Q000378:metabolism; D001924:Brain Concussion / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D003037:Cobalt Radioisotopes; D004569:Electroencephalography; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008081:Liposomes; D008297:Male; D009460:Neurologic Examination; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000493:pharmacokinetics / Q000627:therapeutic use*
D003037:Cobalt Radioisotopes; D008081:Liposomes; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase