Functional Recovery of Carbon Nanotube/Nafion Nanocomposite in Rat Model of Spinal Cord Injury.

BACKGROUND: Acute spinal cord injury (ASCI) can lead to paraplegia or quadriplegia, the treatment of which has been a major problem. New therapeutic approaches in developing carbon nanotubes (CNT) functionalized with the Nafion nanocomposite, a sulfonated tetrafluoroethylene copolymer, have been shown to increase the length of selected neurites in vitro. OBJECTIVE: We hypothesized that the administration of the CNT/Nafion nanocomposite after experimental SCI will promote regeneration of axons into the lesion cavity and the functional recovery of the hind limbs in a rat model. METHODS: To evaluate this hypothesis through this experimental research paper, transection SCI was induced at the T9-T10 vertebral level in adult female rats. One week after transection, the epicenter of the lesion was injected with 25 lL of vehicle (saline), or 1 lg/mL, 10 lg/mL, or 100 lg/mL of CNT/Nafion nanocomposite. Behavioral analysis was carried out by assessing tail flick, chronic pain or mechanical allodynia, motor coordination, and the results of the rotarod test performed pre- and post-surgery, on days 3, 7, 14, 21 and 28, using the tail flick analysis, Noldus CatWalk gait analysis, open-field locomotor test, and Rotarod test. At 28 days post-injection, the rats were euthanized and spinal cord tissue was extracted. RESULTS: We found that post-SCI, administration of the CNT/Nafion nanocomposite resulted in decreased lesion volume, increased neurofilament-positive fibers and corticospinal tract fibers in the lesion, and no increase in reactive gliosis (P < 0.001). Additionally, post-SCI administration of CNT/Nafion nanocomposite induced a modest improvement in hind limb locomotor recovery without inducing hyperalgesia. CONCLUSION: These data suggest that the CNT/Nafion nanocomposite may be an effective material to promote axonal repair and regeneration after SCI.

An extended-release formulation of desferrioxamine for subcutaneous administration.

Desferrioxamine mesylate (DFO) remains the first line iron chelating agent. Since it has a short half-life and poor absorption through the gastrointestinal tract, DFO must be administered parenterally, usually by daily subcutaneous infusion administered over 8-12 h. The objective of this paper was the development of multivesicular liposome (depofoam) for the extended-release of DFO and study of iron excretion efficiency compared to the free form of DFO. Depofoam particles were characterized by their morphology, particle size, capture volume, and in vitro release. Also, in vivo activity of this formulation in iron overload rats was studied. The in vitro studies in 0.9% sodium chloride at 37 degrees C showed that the multivesicular liposomes released DFO slowly over several days without a rapid initial release, and 57% of DFO was released in 9 days. Administration of a single dose of 100 mg/kg of an optimized Depo-DFO formulation in an iron overload rats, as a single bolus subcutaneous injection, led to significant elevation of urinary iron excretion at the first day that were maintained at levels of more than 110 microg/kg for 3 days. Administration of the unencapsulated DFO at the same dose resulted in elevation of urinary iron excretion in the first day (approximately 73% amount of iron excretion by Depo-DFO) followed by a quick decline to base line levels in the second day. The total urinary iron excreted by Depo-DFO is 3-times greater than that elicited by DFO. In conclusion, Depo-DFO appears to have potential usefulness as an extended-release formulation of DFO.

In vivo measurement of noradrenaline in the locus coeruleus of rats during the formalin test: a microdialysis study.

The locus coeruleus is involved in the regulation of the sense of pain. To demonstrate the changes in noradrenaline level in the locus coeruleus during the formalin test, a microdialysis probe was implanted into the left locus coeruleus of rats. Formalin was subcutaneously injected into the plantar surface of the right hind paw and pain ratings were recorded. The concentrations of noradrenaline and its metabolite 3-methoxy-4-hydroxyphenylethylenglycol (MHPG) were measured. The results showed an almost four-fold elevation in noradrenaline release in the early phase of the formalin test; levels return to baseline in the late phase. Levels of MHPG changed in a similar fashion.