Protocol paper: kainic acid excitotoxicity-induced spinal cord injury paraplegia in Sprague-Dawley rats.

BACKGROUND: Excitotoxicity-induced in vivo injury models are vital to reflect the pathophysiological features of acute spinal cord injury (SCI) in humans. The duration and concentration of chemical treatment controls the extent of neuronal cell damage. The extent of injury is explained in relation to locomotor and behavioural activity. Several SCI in vivo methods have been reported and studied extensively, particularly contusion, compression, and transection models. These models depict similar pathophysiology to that in humans but are extremely expensive (contusion) and require expertise (compression). Chemical excitotoxicity-induced SCI models are simple and easy while producing similar clinical manifestations. The kainic acid (KA) excitotoxicity model is a convenient, low-cost, and highly reproducible animal model of SCI in the laboratory. The basic impactor approximately cost between 10,000 and 20,000 USD, while the kainic acid only cost between 300 and 500 USD, which is quite cheap as compared to traditional SCI method. METHODS: In this study, 0.05 mM KA was administered at dose of 10 µL/100 g body weight, at a rate of 10 µL/min, to induce spinal injury by intra-spinal injection between the T12 and T13 thoracic vertebrae. In this protocol, detailed description of a dorsal laminectomy was explained to expose the spinal cord, following intra-spinal kainic acid administration at desired location. The dose, rate and technique to administer kainic acid were explained extensively to reflect a successful paraplegia and spinal cord injury in rats. The postoperative care and complication post injury of paraplegic laboratory animals were also explained, and necessary requirements to overcome these complications were also described to help researcher. RESULTS: This injury model produced impaired hind limb locomotor function with mild seizure. Hence this protocol will help researchers to induce spinal cord injury in laboratories at extremely low cost and also will help to determine the necessary supplies, methods for producing SCI in rats and treatments designed to mitigate post-injury impairment. CONCLUSIONS: Kainic acid intra-spinal injection at the concentration of 0.05 mM, and rate 10 µL/min, is an effective method create spinal injury in rats, however more potent concentrations of kainic acid need to be studied in order to create severe spinal injuries.

Effects of Different Scan Duration on Brain Effective Connectivity among Default Mode Network Nodes.

BACKGROUND: Resting-state functional magnetic resonance imaging (rs-fMRI) can evaluate brain functional connectivity without requiring subjects to perform a specific task. This rs-fMRI is very useful in patients with cognitive decline or unable to respond to tasks. However, long scan durations have been suggested to measure connectivity between brain areas to produce more reliable results, which are not clinically optimal. Therefore, this study aims to evaluate a shorter scan duration and compare the scan duration of 10 and 15 min using the rs-fMRI approach. METHODS: Twenty-one healthy male and female participants (seventeen right-handed and four left-handed), with ages ranging between 21 and 60 years, were recruited. All participants underwent both 10 and 15 min of rs-fMRI scans. The present study evaluated the default mode network (DMN) areas for both scan durations. The areas involved were the posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC), left inferior parietal cortex (LIPC), and right inferior parietal cortex (RIPC). Fifteen causal models were constructed and inverted using spectral dynamic causal modelling (spDCM). The models were compared using Bayesian Model Selection (BMS) for group studies. RESULT: The BMS results indicated that the fully connected model was the winning model among 15 competing models for both 10 and 15 min scan durations. However, there was no significant difference in effective connectivity among the regions of interest between the 10 and 15 min scans. CONCLUSION: Scan duration in the range of 10 to 15 min is sufficient to evaluate the effective connectivity within the DMN region. In frail subjects, a shorter scan duration is more favourable.

Spinal Cord Injury: Pathophysiology, Multimolecular Interactions, and Underlying Recovery Mechanisms.

Spinal cord injury (SCI) is a destructive neurological and pathological state that causes major motor, sensory and autonomic dysfunctions. Its pathophysiology comprises acute and chronic phases and incorporates a cascade of destructive events such as ischemia, oxidative stress, inflammatory events, apoptotic pathways and locomotor dysfunctions. Many therapeutic strategies have been proposed to overcome neurodegenerative events and reduce secondary neuronal damage. Efforts have also been devoted in developing neuroprotective and neuro-regenerative therapies that promote neuronal recovery and outcome. Although varying degrees of success have been achieved, curative accomplishment is still elusive probably due to the complex healing and protective mechanisms involved. Thus, current understanding in this area must be assessed to formulate appropriate treatment modalities to improve SCI recovery. This review aims to promote the understanding of SCI pathophysiology, interrelated or interlinked multimolecular interactions and various methods of neuronal recovery i.e., neuroprotective, immunomodulatory and neuro-regenerative pathways and relevant approaches.