Nerve Growth Factor Administration Attenuates Cognitive but Not Neurobehavioral Motor Dysfunction or Hippocampal Cell Loss Following Fluid‐Percussion Brain Injury in Rats

Abstract

Lateral fluid‐percussion brain injury in rats results in cognitive deficits, motor dysfunction, and selective hippocampal cell loss. Neurotrophic factors have been shown to have potential therapeutic applications in neurodegenerative diseases, and nerve growth factor (NGF) has been shown to be neuroprotective in models of excitotoxicity. This study evaluated the neuroprotective efficacy of intracerebral NGF infusion after traumatic brain injury. Male Sprague‐Dawley rats received lateral fluid‐percussion brain injury of moderate severity (2.1–2.3 atm). A miniosmotic pump was implanted 24 h after injury to infuse NGF (n = 34) or vehicle (n = 16) directly into the region of maximal cortical injury. Infusions of NGF continued until the animal was killed at 72 h, 1 week, or 2 weeks after injury. Animals were evaluated for cognitive dysfunction (Morris Water Maze) and regional neuronal cell loss (Nissl staining) at each of the three time points. Animals surviving for 1 or 2 weeks were also evaluated for neurobehavioral motor function. Although an improvement in memory scores was not observed at 72 h after injury, animals receiving NGF infusions showed significantly improved memory scores when tested at 1 or 2 weeks after injury compared with injured animals receiving vehicle infusions (p < 0.05). Motor scores and CA3 hippocampal cell loss were not significantly different in any group of NGF‐treated animals when compared with controls. These data suggest that NGF administration, in the acute, posttraumatic period following fluid‐percussion brain injury, may have potential in improving post‐traumatic cognitive deficits.

Combination of growth factor treatment and scaffold deposition following traumatic brain injury has only a temporary effect on regeneration

“…The test is commonly used to evaluate the effect of TBI and potential treatment strategies. Previous studies using growth factor treatment after TBI have shown beneficial effects on MWM performance (Lu et al, 2005;Sinson et al, 1995). The positive effect of EGF infusion and VEGF scaffold that we found in While we found a significant effect of the trauma on MWM performance day 36-39 after injury, we could not see any effect of the treatment at this time point.…”

Neurotrophic Factors

“…The continuous presence of NGF infused for at least 4 weeks appears to be required to prevent degeneration of cholinergic neurons after fimbria-fornix transection [112]. Following lateral FP brain injury in rats, intracerebral NGF infusion in the acute phase beginning at 24 h after injury and lasting until the time of sacrifice (72 h, 1 week, 2 weeks) improved memory (when evaluated at 1 and 2 weeks after injury) but not motor function or hippocampal cell loss [113]. Intraparenchymal NGF infusion for 2 weeks after lateral FP brain injury in rats also reduced memory deficits up to 4 weeks after injury, and concomitantly decreased cholinergic neuronal loss and apoptotic cell death in the medial septum [97], suggesting that the behavioral improvements persist after cessation of NGF administration and that the beneficial effects of NGF may be related to its ability to attenuate traumatically induced apoptotic cell death.…”

Localized cell and drug delivery for auditory prostheses

“…The BDNF infusions reduce vestibular deficits, increase neuronal metabolism, and prevent degeneration of nigral neurons (Altar et al, 1994;Volpe et al, 1998). Intraventricular infusion of nerve growth factor (NGF) has been shown to promote the survival of cholinergic neurons, improve cognitive function, and reduce apoptosis in various rat models of traumatic brain injury (Dixon et al, 1997;Sinson et al, 1995Sinson et al, , 1997. The infusion of basic fibroblast growth factor (bFGF) following brain trauma also helped restore cognitive function (McDermott et al, 1997).…”