Rat Model Of Contusion Injury Research Articles

Diagnosis and Simultaneous Treatment of Musculoskeletal Injury Using H2O2-Triggered Echogenic Antioxidant Polymer Nanoparticles in a Rat Model of Contusion Injury.

Ultrasound is clinically used for diagnosis and interventions for musculoskeletal injuries like muscle contusion, but contrast of ultrasonography still remains a challenge in the field of the musculoskeletal system. A level of hydrogen peroxide (H2O2) is known to be elevated during mechanical tissue damage and therefore H2O2 can be exploited as a diagnostic and therapeutic marker for mechanical injuries in the musculoskeletal system. We previously developed poly(vanillin-oxalate) (PVO) as an inflammation-responsive polymeric prodrug of vanillin, which is designed to rapidly respond to H2O2 and exert antioxidant and anti-inflammatory activities. The primary aim of this study is to verify whether PVO nanoparticles could serve as contrast agents as well as therapeutic agents for musculoskeletal injuries simultaneously. In a rat model of contusion-induced muscle injury, PVO nanoparticles generated CO2 bubbles to enhance the ultrasound contrast in the injury site. A single intramuscular injection of PVO nanoparticles also suppressed contusion-induced muscle damages by inhibiting the expression of pro-inflammatory cytokines and inflammatory cell infiltration. We, therefore, anticipate that PVO nanoparticles have great translational potential as not only ultrasound imaging agents but also therapeutic agents for the musculoskeletal disorders such as contusion.

Accelerating locomotor recovery after incomplete spinal injury

A traumatic spinal injury can destroy cells, irreparably damage axons, and trigger a cascade of biochemical responses that increase the extent of injury. Although damaged central nervous system axons do not regrow well naturally, the distributed nature of the nervous system and its capacity to adapt provide opportunities for recovery of function. It is apparent that activity-dependent plasticity plays a role in this recovery and that the endogenous response to injury heightens the capacity for recovery for at least several weeks postinjury. To restore locomotor function, researchers have investigated the use of treadmill-based training, robots, and electrical stimulation to tap into adaptive activity-dependent processes. The current challenge is to maximize the degree of functional recovery. This manuscript reviews the endogenous neural system response to injury, and reviews data and presents novel analyses of these from a rat model of contusion injury that demonstrates how a targeted intervention can accelerate recovery, presumably by engaging processes that underlie activity-dependent plasticity.

Increased expression of the close homolog of the adhesion molecule l1 in different cell types over time after rat spinal cord contusion

The close homolog of the adhesion molecule L1 (CHL1) is important during CNS development, but a study with CHL1 knockout mice showed greater functional recovery after spinal cord injury (SCI) in its absence. We investigated CHL1 expression from 1 to 28 days after clinically relevant contusive SCI in Sprague-Dawley rats. Western blot analysis showed that CHL1 expression was significantly up-regulated at day 1 and further increased over 4 weeks after SCI. Immunohistochemistry of tissue sections showed that CHL1 in the intact spinal cord was expressed at low levels. By 1 day and through 4 weeks after SCI, CHL1 became highly expressed in NG2(+) cells. Hypertrophic GFAP(+) astrocytes also expressed CHL1 by 1 week after injury. The increase in CHL1 protein paralleled that of NG2 in the first week and GFAP between 1 and 4 weeks after injury. At 4 weeks, NG2(+) /CHL1(+) cells and GFAP(+) /CHL1(+) astrocytes were concentrated at the boundary between residual spinal cord tissue and the central lesion. NF200(+) spinal cord axons approached but did not penetrate this boundary. In contrast, CHL1(+) cells in the central lesion at 1 week and later colabeled with p75 and NG2 and were chronically associated with many NF200(+) axons, presumably axons that had sprouted in association with CHL1(+) Schwann cells infiltrating the cord after contusion. Thus, our study demonstrates up-regulation of CHL1 in multiple cell types and locations in a rat model of contusion injury and suggests that this molecule may be involved both in inhibition of axonal regeneration and in recovery processes after SCI.

Ultrastructural scoring of graded acute spinal cord injury in the rat.

There is a need for an accurate quantitative histological technique that also provides information on neurons, axons, vascular endothelium, and subcellular organelles after spinal cord injury (SCI). In this paper the authors describe an objective, quantifiable technique for determining the severity of SCI. The usefulness of ultrastructural scoring of acute SCI was assessed in a rat model of contusion injury. Spinal cords underwent acute contusion injury by using varying weights to produce graded SCI. Adult Wistar rats were divided into five groups. In the first group control animals underwent laminectomy only, after which nontraumatized spinal cord samples were obtained 8 hours postsurgery. The weight-drop technique was used to produce 10-, 25-, 50-, and 100-g/cm injuries. Spinal cord samples were also obtained in the different trauma groups 8 hours after injury. Behavioral assessment and ultrastructural evaluation were performed in all groups. When the intensity of the traumatic injury was increased, behavioral responses showed a decreasing trend. A similar significant negative correlation was observed between trauma-related intensity and ultrastructural scores. In the present study the authors characterize quantitative ultrastructural scoring of SCI in the acute, early postinjury period. Analysis of these results suggests that this method is useful in evaluating the degree of trauma and the effectiveness of pharmacotherapy in neuroprotection studies.

Effect of kynurenate on functional deficits resulting from traumatic spinal cord injury

The potential role of excitatory amino acid (EAA) receptors in spinal cord trauma was examined in a standardized rat model of contusive injury. EAA antagonists were administered in a split-dose protocol with half given 5 min prior to and the remainder 15 min after contusion produced at the T8 vertebral level. Hindlimb function was assessed using a battery of tests of reflex and more complex behaviors at 1 day after injury and weekly thereafter through 4–8 weeks. Functional deficits were compared for groups administered intravenous MK 801 (1 mg/kg), dextromethorphan (10 mg/kg) and kynurenate (300 mg/kg) or the vehicle, saline, alone. In addition, possible effect of the drugs themselves on hindlimb function were assessed in uninjured controls. None of the drugs produced more than transient effect on uninjured rats. In contused rats, only kynurenate produced significant reductions in functional deficits as compared to saline controls. Significant improvement of hindlimb function was also observed when the thoracic cord was locally perfused with kynurenate via intrathecal cannulas and when kynurenate was directly infused into the contusive injury site by stereotaxic microinjection. Using the latter route of administration, a dose-dependent effect of kynurenate (100, 200 and 400 nmol) on the ability of contused rats to use their hindlimbs in locomotion was demonstrated. The highest dose also resulted in a significant reduction in overall functional deficits from 1 week through 1 month and at 2 months after injury. Our results support the hypothesis that EAA receptors at or near the injury site are involved in producing a proportion of the overall functional deficits stemming from traumatic injury. In addition, the efficacy of the broad spectrum antagonist of EAA receptors, kynurenate, and the absence of effect of the NMDA receptor antagonists, MK 801 or dextromethorphan, suggests than non-NMDA receptors may play a hitherto unappreciated role in secondary injury after spinal cord contusion.

Implantation of neuronal suspensions into contusive injury sites in the adult rat spinal cord

Implants of various types of neuronal and nonneuronal tissue have shown promise for the amelioration of certain disorders of the adult mammalian brain. Implants may also have therapeutic potential for some lesions of the spinal cord. To examine the feasibility of implantation for clinically relevant spinal cord injuries, we have implanted cells into injury sites produced by a well-characterized and standardized rat model of contusive injury. To reduce the possibility of the implantation procedure itself causing damage to the spinal cord, the tissue was dissociated and a suspension of cells introduced into the cord via a small bore needle. To test the implantation procedure, dissociated adult rat dorsal root ganglia were used because of the ease with which these neurons could be distinguished after implantation. The extent to which functional deficits were produced or exacerbated by the implantation procedure was assessed by behavioral tests of groups of rats that had been implanted (implant controls), contused (injury only) or contused and implanted (injury-implant). Survival of the implanted neurons was assessed by quantitative morphological analysis of histological sections taken through the injury/implant sites at different times following injury. In addition, the histopathology of the contusive injury sites was compared for rats that had or had not received immediate or delayed implants. Results indicated that cell suspensions could be implanted into the spinal cord without causing a functional deficit in an otherwise uninjured animal or exacerbating a standardized incomplete contusive injury. Implanted neurons survived for at least 4 weeks in all contusion sites whether implantation was performed immediately following injury or after a delay of 1 week.(ABSTRACT TRUNCATED AT 250 WORDS)