Intranasally applied human olfactory mucosa neural progenitor cells migrate to damaged brain regions.

Aim: To determine if intranasally administered olfactory mucosa progenitor cells (OMPCs) migrate to damaged areas of brain.

Materials & Methods: Rowett Nude (RNU) adult rats were injured using the Marmarou model then 2 weeks later received intranasally-delivered human OMPC. After 3 weeks, rats were sacrificed and brain sectioned.

Baclofen Solution for Low-Volume Therapeutic Delivery.

Objectives: Baclofen is a zwitterion molecule where increased ions in the excipient increase the solubility. We developed baclofen in a stable solution similar to cerebrospinal fluid (CSF) without bicarbonate and proteins to improve the solubility of the baclofen and to reduce the potential toxicity to the central nervous system (CNS) and subarachnoid space. The objective is to develop a solution of baclofen wherein baclofen is solubilized in a multivalent physiological ion solution such as artificial cerebrospinal fluid (aCSF) at a concentration from 2 mg/cc to 10 mg/cc.

Targeted ablation of mesenteric projecting sympathetic neurons reduces the hemodynamic response to pain in conscious, spinal cord-transected rats.

Individuals with spinal cord injuries above thoracic level 6 (T(6)) experience episodic bouts of life-threatening hypertension as part of a condition termed autonomic dysreflexia. The paroxysmal hypertension can be caused by a painful stimulus below the level of the injury. Targeted ablation of mesenteric projecting sympathetic neurons may reduce the severity of autonomic dysreflexia by reducing sympathetic activity.

Olfactory mucosal autografts and rehabilitation for chronic traumatic spinal cord injury.

Background/objective: Basic science advances in spinal cord injury (SCI) are leading to novel clinical approaches. The authors report a prospective, uncontrolled pilot study of the safety and outcomes of implanting olfactory mucosal autografts (OMA) in 20 patients with chronic, sensorimotor complete or motor complete SCI.

Methods: Seven paraplegic and 13 tetraplegic subjects (17 men and 3 women; 19-37 years old) who sustained a traumatic SCI 18 to 189 months previously (mean = 49 months) were enrolled.

Targeted ablation of cardiac sympathetic neurons reduces resting, reflex and exercise-induced sympathetic activation in conscious rats.

Cholera toxin B subunit conjugated to saporin (SAP, a ribosomal inactivating protein that binds to and inactivates ribosomes) was injected in both stellate ganglia to evaluate the physiological response to targeted ablation of cardiac sympathetic neurons. Resting cardiac sympathetic activity (cardiac sympathetic tonus), exercise-induced sympathetic activity (heart rate responses to graded exercise), and reflex sympathetic activity (heart rate responses to graded doses of sodium nitroprusside, SNP) were determined in 18 adult conscious Sprague-Dawley male rats. Rats were randomly divided into the following three groups (n = 6/group): 1) control (no injection), 2) bilateral stellate ganglia injection of unconjugated cholera toxin B (CTB), and 3) bilateral stellate ganglia injection of cholera toxin B conjugated to SAP (CTB-SAP).

Functional recovery in rats with chronic spinal cord injuries after exposure to an enriched environment.

Background/objective: The objective of this study was to determine the effect of environmental enrichment on the sensorimotor function of rats with chronic spinal cord injuries.

Design: Adult Sprague-Dawley rats received a contusive injury of moderate severity at vertebral level T8 using a weight-drop device. Three months after injury, 1 randomized group (n = 16) of rats was placed in an enriched environment, whereas the control group (n = 16) remained housed in standard laboratory cages (2/cage).

Olfactory mucosa autografts in human spinal cord injury: a pilot clinical study.

Background/objective: Olfactory mucosa is a readily accessible source of olfactory ensheathing and stem-like progenitor cells for neural repair. To determine the safety and feasibility of transplanting olfactory mucosa autografts into patients with traumatically injured spinal cords, a human pilot clinical study was conducted.

Methods: Seven patients ranging from 18 to 32 years of age (American Spinal Injury Association [ASIA] class A) were treated at 6 months to 6.

Enhanced functional recovery from spinal cord injury following intrathecal or intramuscular administration of poliovirus replicons encoding IL-10.

Poliovirus-based vectors (replicons) have been shown to maintain the in vitro tropism of poliovirus for motor neurons of the CNS. To determine if replicons could be effective for delivery of potentially beneficial proteins to the CNS, we have constructed and characterized a replicon encoding IL-10. IL-10 was rapidly produced in tissue culture cells following in vitro infection with replicons encoding IL-10.

Gene expression in the muscle and central nervous system following intramuscular inoculation of encapsidated or naked poliovirus replicons.

The spread of intramuscularly inoculated poliovirus to the central nervous system (CNS) has been documented in humans, monkeys, and mice transgenic for the human poliovirus receptor. Poliovirus spread is thought to be due to infection of the peripheral nerve and retrograde transport of poliovirus through the axon to the neuron cell body, where final virus uncoating occurs and translation/replication ensues. In previous studies, we have shown that polio-based vectors (replicons) can be used for gene delivery to motor neurons of the CNS.