Date of Award


Degree Type


Degree Name

Doctor of Philosophy (PhD)


Basic Medical Sciences

First Advisor

Richard Ben Borgens

Committee Chair

Jianming Li

Committee Co-Chair

Richard Ben Borgens

Committee Member 1

Stephen R. Byrn

Committee Member 2

Youngnam Cho

Committee Member 3

Linjie Pan


In the U.S., about 200,000 people are currently living with spinal cord injury (SCI). An estimated of 50%-70% of all SCI cases occurs in the range of ages between 15-35 years old. The destructive neurotrauma results in the majority of adult disability, even after patients suffering with SCI survived from the acute death. There are two stages involved in the progression of SCI, the primary stage and the secondary stage. The primary stage is mainly the mechanical damage to the central nervous system. The rapid collapse of the integrity of cell membrane and tissue is often one of the initial onsets. Centered by the cascade of biochemical disruption, such as aldehyde toxins, the secondary injury is responsible for the major clinical deficits in sensory and motor functions. Available pharmacological treatment for SCI includes high doses of steroids. However, the side effects of steroid therapy leave patients more susceptible for complications, such as infections, chronic pain and blood clots. The absence of "standard of care" have triggered waves of intense research leading to "finding a cure for SCI". Based on our previous successful explorations of the neuroprotection by chitosan and chitosan nanoparticles (Chi-NPs) in SCI related cell and tissue studies, we further investigated the neuroprotective effects based on two major characteristics of chitosan: (1) molecular weight (MW) and (2) degree of acetylation (DA). Our results demonstrated that chitosan polymer blocked the random exchange of a probe, tetramethyl-rodamine (TMR) and an endogenous protein, lactate dehydrogenase (LDH), across mechanically compromised cell membrane, while a significant difference of the membrane "sealing" effect was not suggested among different MWs and DAs of chitosan polymer. A similar affinity of FITC-chitosan polymer at intact and injured spinal tissues was also suggested. To push the use of chitosan a step towards clinical tests, we incorporated the advantage of nanomedicine with our "promising chitosan material". Different factors were investigated during the formation and the storage of Chi F-NPs. Two types of Chi-NPs (chitosan-triphosphate, Chi-TPPNPs and chitosan-dextran sulfate, Chi-DSNPs) were synthesized, with a range of size at 100-300nm and zeta-potentials of 30.65mV and -47.4mV, based on an ionic gelation method. Chi-DSNPs were shown to rescue necrotic BV-2 cells induced by a short incubation of hydrogen peroxide at 5.5mM. In addition, the conduction of somatosensory evoked potentials (SSEPs) through the lesion produced by the compression injury was partially restored after 1 week of the subcutaneous administration of Chi-DSNPs. We also found that polyethylene glycol (PEG)-coated silica NPs were significantly accumulated at the compression injured spinal tissues. The affinity of NPs at severed cell membranes was guided by PEG. Our experimental findings suggested that chitosan and Chi-NPs provided neuroprotective effects using both in vitro and in vivo models.