Traumatic brain injury induced neuroprotection of retinal ganglion cells to optic nerve crush.
Optic nerve crush injury leads to death of retinal ganglion cells (RGCs), both as a direct result of the primary injury and via secondary degeneration induced by neurotoxins secreted by dying RGCs. Studies have shown that, if optic nerve crush is preceded by an unrelated injury to another part of the central nervous system, for example, the spinal cord, the ensuing T cell-mediated protective autoimmunity results in a significant increase in RGC survival. In this study, we used the controlled cortical impact paradigm to induce unilateral traumatic brain injury (TBI) in rats at different times before they were contralaterally subjected to a mild optic nerve crush. Survival of RGCs, assessed 2 weeks after crush injury, was significantly increased when the crush was inflicted 11 days after TBI, but not when the two injuries were concomitant. The beneficial effect was unaffected by injection of low-dose methylprednisolone MP (1 mg/kg), but was inhibited after a high-dose injection (30 mg/kg). Brain-derived neurotrophic factor (BDNF) mRNA, assayed at intervals after TBI, was increased in the retina ipsilateral to TBI but decreased in the contralateral retina. BDNF peaked 1 day after TBI, decreased on day 11, and rose again on day 21. It thus seems that brain injury sustained a certain time before optic nerve injury has a protective effect on RGC survival. This neuroprotective effect, which appears unrelated to retinal BDNF, is inhibited by high-dose MP, commonly used clinically to treat traumatic optic neuropathy.
Ben Simon
Guy J
GJ
Jules Stein Eye Institute and Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA. guybensimon@gmail.com
Hovda
David A
DA
Harris
Neil G
NG
Gomez-Pinilla
Fernando
F
Goldberg
Robert A
RA
D000818:Animals; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D008297:Male; D009409:Nerve Crush; D020221:Optic Nerve Injuries / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology*
D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger