Effects of Exercise Following Lateral Fluid Percussion Brain Injury in Rats

Restorative Neurology and Neuroscience 12 (1998) 41–460922-6028/98/$8.00 © 1998, IOS Pressrnn3798–05–08–09–35

1.IntroductionAn important question facing rehabilitation specialists ishow to maximize functional recovery after traumatic braininjury (TBI). A variety of functional deficits may be presentafter TBI, but impairments in information processing, per-ceptual function, and memory are the most common [27].Numerous studies have demonstrated that exercise may beimportant for maintaining cognitive and memory function inhumans (for review see [10]). Although the exact physiolog-ical mechanisms underlying these improvements are un-

* Correspondence to: Ramona Hicks, Ph.D., University of Kentucky, CAHPBldg., Rm. 213, Lexington, KY 40536-0003, USA, Tel.: +16063231497

known, several molecular events in the brain that are associ-ated with physical activity may be important. In humans, moderate to high intensity exercise increasesregional cerebral blood flow [22,47], as well as plasma lev-els of noradrenaline and serotonin, neurotransmitters that arethought to be associated with memory storage and retrieval[9]. In animal studies, exercise has been linked to an increasein neuronal activity in the hippocampus, as demonstrated byelevations in extracellular lactate [5]. In aged rats, exerciseincreases antioxidant enzymes in brain tissue [45]. Exerciseprior to an ischemic injury in gerbils, lowered mortality andattenuated damage in the cortex, striatum, and hippocampus[46]. Alterations in neurotrophic factor levels have also been

Effects of Exercise Following Lateral Fluid Percussion Brain Injury in RatsRamona R. Hicks,1 Arden Boggs,1 Denise Leider,1 Philip Kraemer,2 Russell Brown,2 Stephen W. Scheff,3 and Kim B. Seroogy4

Departments of 1Physical Therapy, 2Psychology, 3Sanders-Brown Center on Aging, and 4Anatomy and Neurobiology, University of Kentucky,Lexington Kentucky, USA

Received 5 November 1997; revised 22 January 1998; accepted 26 January 1998

AbstractPrevious studies have suggested that brain-derived neurotrophic factor (BDNF) is involved in memory and learning, and maybe neuroprotective following various brain insults. Exercise has been found to increase BDNF mRNA levels in various brainregions, including specific subpopulations of hippocampal neurons. In the present study, we were interested in whether follow-ing traumatic brain injury, exercise could increase BDNF mRNA expression, attenuate neuropathology, and improve cognitiveand neuromotor performance. We subjected adult male Sprague-Dawley rats to a fluid percussion brain injury, followed byeither 18 days of treadmill exercise or handling. Spatial memory was evaluated in a Morris Water Maze (MWM) and motorfunction was evaluated with a battery of neuromotor tests. Neuropathology was evaluated by measuring the cortical lesion vol-ume and the extent of neuronal loss in the hippocampus. Expression of BDNF mRNA in the hippocampus was assessed with in

situ hybridization and densitometry. Hybridization signal for BDNF mRNA was significantly increased bilaterally in the exer-cise group in hippocampal regions CA1 and CA3 (p < 0.05), but not in the granule cell layer of the dentate gyrus. No significantdifferences were observed between the groups in neuropathology, spatial memory, or motor performance. This study suggeststhat after traumatic brain injury, exercise elevates BDNF mRNA in specific regions of the hippocampus.

Keywords: brain-derived neurotrophic factor, cognition, traumatic brain injury42R. R. Hicks et al. / Restorative Neurology and Neuroscience 12 (1998)

rnn3798–05–08–09–35associated with exercise. Following 2–7 days of exercise onfree-running wheels, brain-derived neurotrophic factor (BD-NF), nerve growth factor (NGF), and basic fibroblast growthfactor (bFGF) were increased in various regions of the hip-pocampus and cortex in rats [15,34,35]. BDNF is the most prevalent neurotrophin in the brain, withespecially high levels in the neocortex, cerebellum and hip-pocampus [19,28]. Although the function of BDNF is incom-pletely understood, it appears to play a role in long-term po-tentiation (LTP) and memory formation [8,12,24], and activ-ity-dependent neuroplasticity [13,30,39]. Housing rats in anenriched environment not only improves spatial memory[16,32] and increases synaptic density and branching in thehippocampus [23], it also up-regulates BDNF mRNA [11].The present study tested whether exercise following a lateralfluid percussion (FP) brain injury could increase BDNFmRNA expression in the hippocampus and attenuate the neu-ropathology and behavioral deficits that are associated withthis model of experimental brain injury in rats [17,43].