Biomedical subjects

Vernon W Lin

Publications and source records attributed to Vernon W Lin.

7 recordsLinked to original sources

PubMed2006

Re-growth of catecholaminergic fibers and protection of cholinergic spinal cord neurons in spinal repaired rats.

The extent of re-growth of catecholaminergic fibers, the survival of cholinergic neurons and the degree of autonomic dysreflexia were assessed in complete spinal cord-transected adult rats that received a repair treatment of peripheral nerve grafts and acidic fibroblast growth factor (aFGF). The rats were randomly divided into three groups: (1) sham control group (laminectomy only); (2) spinal cord transection at T8 (transected group); and (3) spinal cord transection at T8, followed by aFGF treatment and peripheral nerve graft (repaired group). The spinal cords and brains of all rats were collected at 6 months post-surgery. Immunohistochemistry for tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH), and fluoro-gold (FG) retrograde tracing were used to evaluate axon growth across the damage site, and immunocytochemistry for choline acetyl transferase (ChAT) was used to evaluate cholinergic neuronal cell survival following the injury and treatment. When comparing with the transected group, the repaired group showed: (1) lower elevation of mean arterial pressure during colorectal distension; (2) retrogradely labeled neurons in the hypothalamus, zona incerta, subcoeruleus nuclei and rostral ventrolateral medulla following application of FG below the repair site; (3) the presence of TH- and DBH-labeled axons below the lesion site; (4) higher numbers of ChAT-positive neurons in ventral horn and intermediolateral column near the lesion site. We conclude that peripheral nerve graft and aFGF treatments facilitate the re-growth of catecholaminergic fibers, also protect sympathetic preganglionic neurons and spinal motor neurons, and reduce autonomic dysfunction in a T-8 spinal cord-transected rat model.

Acetylcholine↗

PubMed2004

Effects of nerve graft on nitric oxide synthase, NAD(P)H oxidase, and antioxidant enzymes in chronic spinal cord injury.

Oxidative stress and nitrosative stress play important roles in the pathogenesis of secondary spinal cord injury. Recently, we demonstrated that peripheral nerve grafts (PNG) with acidic fibroblast growth factor (aFGF) partially restore hind limb locomotion in adult rats with completely transected spinal cords. This study investigated the protein abundances of the superoxide (O2*)-generating enzyme nicotinamide adenine dinucleotide (phosphate) oxidase (NAD(P)H oxidase; gp91phox subunit), nitric oxide synthases (NOS), antioxidant enzymes, superoxide dismutases (Cu Zn SOD, Mn SOD), catalase, and glutathione peroxidase (GPX) as well as nitrotyrosine in the spinal cord tissue 4 months after spinal cord transection in rats with and without PNG and aFGF. The protein abundances of the gp91phox subunit of NAD(P)H oxidase, Mn SOD, catalase, GPX, eNOS, and nitrotyrosine were significantly upregulated, whereas Cu Zn SOD and nNOS were unchanged in the injury group compared to the sham controls. The nerve graft with aFGF treated group showed significantly better hind limb locomotion recovery than the injury group. Although the protein abundances of gp91phox, nitrotyrosine, and Cu Zn SOD were similar in the treated group (nerve graft with aFGF) compared to the injury group, Mn SOD, GPX, catalase, and eNOS protein abundances were significantly higher, whereas nNOS was markedly lower in the treated group. We conclude that the combination of nerve graft and aFGF enhances the local antioxidant defense system after spinal cord transection in rats.

Animals↗

PubMed2004

NAD(P)H oxidase, superoxide dismutase, catalase, glutathione peroxidase and nitric oxide synthase expression in subacute spinal cord injury.

Primary trauma to the spinal cord triggers a cascade of cellular and molecular events that promote continued tissue damage and expansion of the lesion for extended periods following the initial injury. Oxidative and nitrosative stresses play an important role in progression of spinal cord injury (SCI). In an attempt to explore the biochemical origin of oxidative/nitrosative stress associated with secondary SCI, we studied expression of the superoxide (O2*-)-generating enzyme, NAD(P)H oxidase, antioxidant enzymes [superoxide dismutase (CuZn SOD, Mn SOD), catalase, glutathione peroxidase (GPX)], nitric oxide synthases (NOS) and a byproduct of NO-O2*- interaction (nitrotyrosine) in the spinal cord tissues of rats 16 h and 14 days after surgical resections of a 5-mm segment of the cord below T8 or sham-operation. Immunodetectable NAD(P)H oxidase subunits (gp91phox and P67phox), Mn SOD, inducible NOS (iNOS), endothelial NOS (eNOS), and nitrotyrosine were elevated in the transected cords on day 1 and day 14. Neuronal NOS (nNOS) was unchanged on day 1 and significantly depressed on day 14. GPX was unchanged on day 1 and significantly elevated on day 14. Catalase was unchanged in the cord tissue surrounding the transection site at both points. Thus, concurrent upregulations of NAD(P)H oxidase, eNOS and iNOS (but not nNOS), work in concert to maintain oxidative and nitrosative stress in the injured cord tissue.

Acute Disease↗

PubMed2004

Functional magnetic ventilation in dogs.

OBJECTIVE: To investigate the efficacy of the magnetic stimulation of inspiratory muscles as an alternative to mechanical ventilation and functional electric stimulation. DESIGN: A prospective before-after trial. SETTING: Functional magnetic stimulation laboratory in a Veterans Administration health care system. ANIMALS: Six male mongrel dogs, each weighing between 25 and 35 kg. INTERVENTIONS: Commercially available magnetic stimulators with a round magnetic coil were used. The center of the magnetic coil was placed posteriorly over the C5-7 vertebrae of the spinal cord transected dogs. Magnetic stimulation parameters were set at 80% intensity, 20 Hz, and a 1.2-second on and 3.8-second off pulse train. MAIN OUTCOME MEASURES: The major outcomes were changes in tidal volume (VT), tracheal pressure (Ptr), and arterial partial pressure of carbon dioxide (PaCO2) and oxygen sustained by magnetic stimulation over time. RESULTS: The average Vt and Ptr produced during functional magnetic ventilation (FMV) were.47+/-.07 L and -4.7+/-.51 cmH2O, respectively. Blood gas data showed that PaCO2 increased from a baseline of 33 to 75 mmHg, whereas pH decreased from 7.33 to 6.99 at the end of the 1-hour FMV period. CONCLUSIONS: FMV was achieved for 2 hours in dogs with C2 spinal cord transection. Additional refinements in magnetic stimulation are needed to improve ventilation in animals.

Analysis of Variance↗

PubMed2004

Motor recovery and anatomical evidence of axonal regrowth in spinal cord-repaired adult rats.

Behavioral assessments of hindlimb motor recovery and anatomical assessments of extended axons of long spinal tracts were conducted in adult rats following complete spinal cord transection. Rats were randomly divided into 3 groups: 1) sham control group (laminectomy only; n = 12); 2) transection-only group, spinal cord transection at T8 (n = 20); and 3) experimental treatment group, spinal cord transection at T8, with peripheral nerve grafts (PNG) and application of acidic fibroblast growth factor (aFGF) (n = 14). The locomotor behavior and stepping of all rats were analyzed over a 6-month survival time using the Basso, Beattie, Bresnahan (BBB) open field locomotor test and the contact placing test. Immunohistochemistry for serotonin (5-HT), anterograde tracing with biotinylated dextran amine (BDA), and retrograde tracing with fluoro-gold were used to evaluate the presence of axons below the damage site following treatment. When compared with the transection-only group, the nerve graft with the aFGF group showed 1) significant improvement in hindlimb locomotion and stepping, 2) the presence of 5-HT-labeled axons below the lesion site at lumbar cord level (these were interpreted as regenerated axons from the raphe nuclei), 3) the presence of anterograde BDA labeling of corticospinal tract axons at the graft site and below, and 4) fluoro-gold retrograde labeling of neuron populations in motor cortex and in red nucleus, reticulospinal nuclei, raphe nuclei, and vestibular nuclei. We conclude that peripheral nerve grafts and aFGF treatments facilitate the regrowth of the spinal axons and improve hindlimb function in a T-8 spinal cord-transected rat model.

Animals↗

PubMed2002

Peripheral nerve grafts and aFGF restore partial hindlimb function in adult paraplegic rats.

The purpose of this study was to evaluate the degree of functional recovery in adult rats with completely transected spinal cord following experimental treatment regimens that include implantation of peripheral nerve segments and local application of acidic fibroblast growth factor (aFGF). Rats were randomly divided to five groups: (1) spinal cord transection, (2) spinal cord transection and aFGF treatment, (3) spinal cord transection and peripheral nerve grafts, (4) spinal cord transection, aFGF treatment, and peripheral nerve grafts, and (5) sham control (laminectomy only). The locomotor behavior of all rats was analyzed by the Basso, Beattie and Bresnahan (BBB) open field locomotor test over the six months survival time. Immunohistochemisty for neurofilament protein, and somatosensory (SSEP) and motor evoked potentials (MEP) were used to evaluate axon growth across the damage site following the different treatments. The results show four principal findings: (1) Only the combination of peripheral nerve grafts and aFGF treatment improved hindlimb locomotor function after spinal cord transection. (2) The SSEP and MEP demonstrated electrophysiological evidence of both sensory and motor information crossing the damaged site, but only in the combined nerve grafts and aFGF treatment rats. (3) Immunostaining demonstrated neurofilament positive axons extending through the graft area and into distal end of spinal cord, but only in the group with combined nerve grafts and aFGF treatment. (4) Retransection of group 4 rats eliminated the behavioral recovery, MEP, and SSEP responses, indicating that the improvement of hindlimb locomotor activity came from supraspinal control. These results demonstrate the ability of the repair strategy combining peripheral nerve grafts and aFGF treatment to facilitate the regeneration of spinal ascending and descending tracts and also recovery of motor behavior following spinal cord injury.

Animals↗

PubMed2002

AFGF promotes axonal growth in rat spinal cord organotypic slice co-cultures.

This study developed a slice culture model system to study axonal regeneration after spinal cord injury. This model was tested in studies of the roles of acidic fibroblast growth factor (aFGF) and peripheral nerve segments in axonal growth between pieces of spinal cord. Transverse sections of P15-P18 Sprague-Dawley rat spinal cord were collected for organotypic slice cultures. Group I consisted of two slices of spinal cord in contact with each other during the culture period. Group II consisted of two slices that were separated by 3 mm and connected by two segments of intercostal nerves. Group III consisted of single slices for studies of neuron survival. Some cultures from each group included aFGF in the culture medium. Bromodeoxyuridine (BrdU) was included in the medium for some cultures. The results showed three principal findings. First, counts of neurofilament-positive cells demonstrated that treatment with aFGF significantly increased the number of surviving neurons in culture. Second, neurofilament immunostaining and DiI tracing demonstrated axons crossing the junction between the two pieces of spinal cord or growing through the intercostal nerve segments, and these axons were seen only in cultures with aFGF treatment. Third, few cells were double stained for neurofilament and BrdU, and these were found only with aFGF treatment. These results demonstrate that (1) organotypic slice cultures present a useful model to study regeneration from spinal cord injury, (2) aFGF rescues neurons and promotes axonal growth in these cultures, and (3) segments of intercostal nerves promote axon growth between slices of spinal cord.

Animals↗