The Effects of Decompression and Exogenous NGF on Compressed Cerebral Cortex

Abstract

Using a rat epidural bead implantation model, we found that compression alone could reduce the overall and individual layer thicknesses of cerebral cortex with no apparent cell death. The dendritic lengths and spine densities of layer II/III and V pyramidal neurons started to decrease within 3 days of compression. Decompression for 14 days resulted in near complete to partial recovery of the cortical thickness and of the dendritic lengths of layer II/III and V pyramidal neurons, depending on the duration of the preceding compression. The recoverability was better following short (3-day) than long (1-or 3-month) periods of compression. The loss of dendritic spines nevertheless persisted. An intraventricular infusion of NGF was performed after decompressing the lesions following 3 days of cortical compression, and this increased the recovery of the spines but not the dendritic length of the cortical pyramidal neurons, nor did it alter the recovery of the cortical thickness. NGF also promoted the increase of the dendritic spines, but not the dendritic length of the cortical pyramidal neurons of normal animals. In short, the data show that a few days of compression alone can cause permanent cortical damage. Exogenous NGF, if applied topically, may restore the dendritic spine density of cortical neurons subjected to compression.

Compression Alters Kinase and Phosphatase Activity and Tau and MAP2 Phosphorylation Transiently while Inducing the Fast Adaptive Dendritic Remodeling of Underlying Cortical Neurons

“…Our model, on the other hand, produces persistent compression in freelymoving rats. The fixed bead size, light and inert nature of the material, ease of handling (Chen et al, 2004), and reproducibility, make this the model of choice for studying the effects of mechanical force in TBI, and it has recently been adopted by other research groups (Lin et al, 2010;Yang et al, 2006). In our model, physical compression did not cause any apparent cell loss (Chen et al, 2003), suggesting that the severe cell loss and cavity formation often associated with TBI likely results from factors other than physical compression.…”

NMDA receptor triggered molecular cascade underlies compression-induced rapid dendritic spine plasticity in cortical neurons

“…2003). In addition, unlike the transient loss of dendritic spines following lateral brain compression (Campbell et al, 2012b), the loss of dendritic spines in our epidural compression model was irreversible when decompressed 3 days later (Chen et al, 2004). This signified a rapid onset and subsequent permanent loss of dendritic spines on the compressed neurons.…”

“…Using rats as a model, we demonstrated that epidural compression of the somatosensory cortex distorted the dendritic arbors of the underlying cortical pyramidal neurons instantaneously and neurons underwent dramatic dendritic reorganization in 3 days (Chen et al, 2003(Chen et al, , 2010a. In addition, dendritic spines on these neurons were also reduced within 3 days (Chen et al, 2003), which was irreversible with delayed decompression (Chen et al, 2004). Since dendritic spines are the sites of excitatory neurotransmission (Gray, 1959) on pyramidal neurons, the main output neurons, of the cerebral cortex, their irreversible loss suggests long-term alteration of neuronal circuits and cognitive dysfunction (Segal, 2005) in patients experienced cerebral compression.…”

Cloning of the eukaryotic expression vector with nerve growth factor in rats and its effects on proliferation and differentiation of mesencephal neural stem cells of fetal rats

“…Similarly, NSCs transfected with NGF genes could markedly promote the growth of processes after differentiation. Transplantation of NSCs carrying NGF into brain tissue could increase the NGF concentration in the injured site and promote the repair of local neuron injury, which is of value in the treatment of central and peripheral nervous system injuries by NGF in future [6] .…”