Neuroscience Research 23 (1995) 185-194 Vascular permeability to growth hormone in the rat central nervous system after focal spinal cord injury. Influence of a new anti-oxidant H 290/Y and age A. MustafaaTb, H.S. Sharma*““, Y. Olsson’, T. Gordhd, P. Thbren”, P.-O. Sjbquiste, P. Roosb, A. Adem’, F. Nyberg” zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPON aDepartment of Pharmaceutical Biosciences, Biomedical Centre. Uppsala University, uppsala, Sweden ‘Division of Drug Dependence. Department of Biochemistry, Biomedical Centre, Uppsala University, uppsak, Sw eden ‘Laboratory zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA of Neuropathology. University Hospital, Uppsala, Uppsala, Sweden ‘Department zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA of Anaesthesiology, University Hospital, Uppsala, Uppsala, Sweden ePharmacology CV, Astra Hassle AB, Miilmial, Sweden tDepartment of Geriatric Medicine. Karolinska Institute, Huadinge Hospital, Hdhge, Sw eden Received 25 April 1995;accepted 6 June 1995 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONM AbStHlCt Vascular permeability to the growth hormone (GH) across the blood-brain barrier (BBB) is unknown. This investigation was undertaken to examine vascular permeability to ‘2SI-labelled rat growth hormone (rGH) in the central nervous system (CNS) of normal animals. Since age and spinal cord injury influences the metabolism of GH, these factors were also included. No statistically significant difference was seen regarding rGH permeability between young (aged 19-21 weeks) and old (age 38-42 weeks) animals. A focal trauma to the cord, produced by an incision into the right dorsal horn of the TlO-11 segments in young animals, increased rGH permeability in several spinal cord segments at 0.5-5.0 h after injury. This permeability increase progressed over time. Similar trauma to old rats resulted in a significantly less increase in rGH permeability in the spinal cord 5 h after the trauma. This indicates that trauma-induced increased permeability of rGH is age-dependent. Pretreatment of normal young animals with a new anti- oxidant (H 290/51) did not influence the rGH permeability. However, the drug prevented the trauma-induced increase of rGH per- meability at 5 h after injury. This indicates that inhibition of lipid peroxidation has some protective effect on trauma-induced increase in rGH permeability. Keywords: Rat growth hormone; Spinal cord injury; Aging; Blood-spinal cord barrier; Blood-brain barrier; H 290151; Lipid peroxi- dation; Anti-oxidant zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA 1. Introduction Growth hormone (GH) is primarily involved in the regulation of somatic growth. However, it also par- ticipates in the control of a number of other physiological processes such as regulation of carbohy- drate and lipid metabolism (Goodman, 1981; Gritching et al., 1983; Davidson, 1987). It is generally believed that GH exerts its effects only * Corresponding author, Laboratory of Neuropathology, Univer- sity Hospital, S-751 85 Uppsala, Sweden. Tel.: +46 I8 24 38 99; Fax: +46 18 24 38 99. on peripheral tissues. However, GH may have some cen- tral effects since there are GH binding sites in the cerebral cortex, hippocampus, hypothalamus, cerebel- lum and the spinal cord (Lai et al., 1991, 1993; Mustafa et al., 1994a,b). Moreover, GH receptor immunoreac- tivity (Lobie et al., 1989) and GH receptor mRNA (Bur- ton et al., 1992) have been identified in different regions of the rat brain. The question has been raised about the origin of the GH that may interact with the observed binding sites. The brain and spinal cord contain very low amounts of GH under normal conditions. Since GH can be detected in rat serum after hypophysectomy (Ho- jvat et al., 1982) it has been suggested that GH is syn- 016%0102/95/W.50 0 1995 Elsevier Science Ireland Ltd. All rights reserved SSDI Ol68-0102(95)00937-O