Protective effects of bFGF against brain injury

• Published in: Japanese Journal of Pharmacology Vol. 71; no. suppl.1; p. 192
• Main Authors: Murayama, Norihito, Masumura, Makoto, Uramoto, Hiroshi, Ohno, Tomochika
• Format: Journal Article
• Language: Japanese; English
• Published: The Japanese Pharmacological Society 1996
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)37007-6

Neuroprotective effects of bFGF were examined in the traumatic injured brains and in primary neurons cultured under different experimental conditions. Male Wistar rats received a surgery of turning the screw into the brain. Brain edema (water contents of ipsilateral cerebral hemispheres) and BBB dysfunction (extension of IgG leakage) developing after the traumatic brain injury (TBI) were measured with time until 7 days. Furthermore, locomotor activity 3 days after TBI was measured. bFGF (5, 25 ng/5 μl) and platelet factor-4 (PF-4, 50 ng/5 μl) were administered into the right lateral ventricle immediately before TBI. Primary neurons from the neocortex and hippocampus of rat fetuses (E 18) were cultured in DMEM containing 10% horse serum. bFGF was applied at the concentrations of 1, 5, 10 and 25 ng/ml 36 hr or 60 hr after seeding. The neuronal damages were induced by glutamate (0.1 mM for 12 hr) and β amyloid peptide 25-35 (βAP, 10 μM for 3 days) applied 12 hr after treatment with bFGF or vehicle. Traumatic neuronal injury in vitro was produced by tearing in the neuronal and glial cell layer, and cultures were then incubated for 24 hrs. bFGF was applied 24 hr before the mechanical injury. A biphasic development of brain edema was observed; the water contents increased with time until day 3, which maintained until day 5, and then increased again to a maximum on day 6 after TBI. In contrast, the extension of IgG leakage increased to a maximum on postoperative day 3, which persisted until day 7. bFGF significantly inhibited TBI-induced edema, whereas PF-4 increased the water content 6 days after TBI. bFGF also prevented BBB dysfunction (IgG leak) and hypoambulation observed 3 days after TBI. Furthermore, expressions of FGF receptor and bFGF were observed 1 and 5 days after TBI. bFGF protected primary cultured neurons from glutamate- and βAP-induced damages in a concentration-dependent manner, which was blocked by pretreatment with actinomycin D, cycloheximide, or PF-4. However, simultaneous application of bFGF with glutamate did not show any neuroprotective effect. Against traumatic neuronal injury in vitro, bFGF also exerted neuroprotective effects and neurite outgrowth at the edge of the tear. These results taken together indicate that bFGF exerts neuroprotective effects against damages in response to mechanical insult.