Methodology Matters: Designing a Pilot Study Guided by Indigenous Epistemologies.

Indigenous individuals and communities have experienced historic and ongoing negative interactions with Western health care and biomedical research. To rebuild trust and mitigate power structures between researchers and Indigenous peoples, researchers can adopt Indigenous epistemologies in methodologies, such as nonhierarchical approaches to relationship. This article shares models developed to bridge Indigenous epistemologies with Western qualitative and quantitative research methods and demonstrates how these epistemologies can be used to guide the authors' development of a pilot study on traumatic spinal cord injury.

Traumatic spinal cord injuries among Aboriginal and non-Aboriginal populations of Saskatchewan: a prospective outcomes study.

Background: People of Aboriginal (Indigenous) ancestry are more likely to experience traumatic spinal cord injury (TSCI) than other Canadians; however, outcome studies are limited. This study aims to compare Aboriginal and non-Aboriginal populations with acute TSCI with respect to preinjury baseline characteristics, injury severity, treatment, outcomes and length of stay. Methods: This was a retrospective analysis of participants with a TSCI who were enrolled in the prospective Rick Hansen Spinal Cord Injury Registry (RHSCIR), Saskatoon site (Royal University Hospital), between Feb. 13, 2010, and Dec. 17, 2016. Demographic, injury and management data were assessed to identify any differences between the populations. Results: Of the 159 patients admitted to Royal University Hospital with an acute TSCI during the study period, 62 provided consent and were included in the study. Of these, 21 self-identified as Aboriginal (33.9%) and 41 as non-Aboriginal (66.1%) on treatment intake forms. Compared with non-Aboriginal participants, Aboriginal participants were younger, had fewer medical comorbidities, had a similar severity of neurologic injury and had similar clinical outcomes. However, the time to discharge to the community was significantly longer for Aboriginal participants (median 104.0 v. 34.0 d, p = 0.016). Although 35% of non-Aboriginal participants were discharged home from the acute care site, no Aboriginal participants were transferred home directly. Conclusion: This study suggests a need for better allocation of resources for transition to the community for Aboriginal people with a TSCI in Saskatchewan. We plan to assess outcomes from TSCI for Aboriginal people across Canada.

Contexte: Au Canada, les personnes d'origine autochtone sont plus susceptibles que les autres de vivre un traumatisme médullaire. Malgré cela, il y a peu d'études sur les conséquences de cet événement. Notre étude visait à comparer les cas de traumatisme médullaire aigu dans les populations autochtones et non autochtones sur plusieurs plans : les caractéristiques initiales des patients, la gravité du traumatisme, la nature du traitement, les issues cliniques et la durée de séjour. Méthodes: Nous avons fait une analyse rétrospective des dossiers de personnes ajoutées au Rick Hansen Spinal Cord Injury Registry (RHSCIR) [Registre des traumatismes médullaires Rick Hansen] entre le 13 février 2010 et le 17 décembre 2016 pour l'établissement de Saskatoon (l'Hôpital universitaire Royal). Nous avons comparé les renseignements de base des patients ainsi que les données sur le traumatisme et la prise en charge afin de cerner toute différence entre les populations. Résultats: Sur les 159 traumatisés médullaires admis à l'Hôpital universitaire Royal pendant la période à l'étude, 62 ont consenti à l'utilisation de leurs données. Parmi eux, 21 s'étaient identifiés comme Autochtones (33,9 %) sur le formulaire d'hospitalisation, et 41 comme non-Autochtones (66,1 %). Par rapport aux non-Autochtones, les Autochtones étaient plus jeunes, avaient moins de comorbidités, présentaient une atteinte neurologique de gravité comparable et connaissaient à peu près le même tableau clinique. Toutefois, le délai avant leur retour en communauté était significativement plus long (médiane : 104,0 jours contre 34,0 jours; p = 0,016). Aucun participant autochtone n'a été renvoyé directement à la maison, alors que 35 % des participants non autochtones sont retournés chez eux en quittant les soins de première ligne. Conclusion: Cette étude montre qu'il faut améliorer la répartition des ressources de retour dans la communauté pour les traumatisés médullaires autochtones de la Saskatchewan. Enfin, nous comptons examiner les répercussions cliniques du traumatisme médullaire chez les Autochtones de partout au Canada.

A reliable method for intracranial electrode implantation and chronic electrical stimulation in the mouse brain.

BACKGROUND: Electrical stimulation of brain structures has been widely used in rodent models for kindling or modeling deep brain stimulation used clinically. This requires surgical implantation of intracranial electrodes and subsequent chronic stimulation in individual animals for several weeks. Anchoring screws and dental acrylic have long been used to secure implanted intracranial electrodes in rats. However, such an approach is limited when carried out in mouse models as the thin mouse skull may not be strong enough to accommodate the anchoring screws. We describe here a screw-free, glue-based method for implanting bipolar stimulating electrodes in the mouse brain and validate this method in a mouse model of hippocampal electrical kindling. METHODS: Male C57 black mice (initial ages of 6-8 months) were used in the present experiments. Bipolar electrodes were implanted bilaterally in the hippocampal CA3 area for electrical stimulation and electroencephalographic recordings. The electrodes were secured onto the skull via glue and dental acrylic but without anchoring screws. A daily stimulation protocol was used to induce electrographic discharges and motor seizures. The locations of implanted electrodes were verified by hippocampal electrographic activities and later histological assessments. RESULTS: Using the glue-based implantation method, we implanted bilateral bipolar electrodes in 25 mice. Electrographic discharges and motor seizures were successfully induced via hippocampal electrical kindling. Importantly, no animal encountered infection in the implanted area or a loss of implanted electrodes after 4-6 months of repetitive stimulation/recording. CONCLUSION: We suggest that the glue-based, screw-free method is reliable for chronic brain stimulation and high-quality electroencephalographic recordings in mice. The technical aspects described this study may help future studies in mouse models.

Acute administration of docosahexaenoic acid increases resistance to pentylenetetrazol-induced seizures in rats.

OBJECTIVE: Docosahexaenoic acid (DHA), an omega-3 fatty acid, has been reported to raise seizure thresholds. The purpose of the present study was to test the acute anticonvulsant effects of unesterified DHA in rats, using the maximal pentylenetetrazol (PTZ) seizure model, and also to examine DHA incorporation and distribution into blood serum total lipids and brain phospholipids and unesterified fatty acids. Sedation was measured to monitor for the potential toxicity of DHA. METHODS: Male Wistar rats received subcutaneous injections of saline, oleic acid (OA), or DHA. An initial pilot study (Experiment 1) established 400mg/kg as an effective dose of DHA in the maximal PTZ seizure test. A subsequent time-response study, using 400mg/kg (Experiment 2), established 1 hour as an effective postinjection interval for administering DHA subcutaneously. A final study (Experiment 3) comprised two different groups. The first group ("seizure-tested rats") received saline, OA, or DHA (400mg/kg) subcutaneously, and were seizure tested in the maximal PTZ test 1 hour later to confirm the seizure latency measurements at that time. The second group ("assay rats") received identical subcutaneous injections of saline, OA, or DHA (400mg/kg). One hour postinjection, however, they were sacrificed for assay rather than being seizure tested. Assays involved the analysis of serum and brain DHA. Sedation was measured in both Experiment 3 groups during the 1-hour period prior to seizure testing or sacrifice. RESULTS: As noted above, 400mg/kg proved to be an effective subcutaneous dose of DHA (Experiment 1), and 1 hour proved to be the most effective injection-test interval (Experiment 2). In Experiment 3, in the seizure-tested animals, subcutaneous administration of 400mg/kg of DHA significantly increased latency to PTZ seizure onset 1 hour postinjection relative to the saline- and OA-injected controls, which did not differ significantly from each other (P>0.05). In the assay animals, no significant effects of treatment on blood serum total lipids or on brain phospholipid or unesterified fatty acid profiles (P>0.05) were observed. There were also no differences in sedation among the three groups (P>0.05). CONCLUSION: DHA increases resistance to PTZ-induced seizures without altering measures of sedation and, apparently, without changing DHA concentrations in serum or brain.

Dietary Omega-3 Polyunsaturated Fatty Acid Deprivation Does Not Alter Seizure Thresholds but May Prevent the Anti-seizure Effects of Injected Docosahexaenoic Acid in Rats.

Background: Brain concentrations of omega-3 docosahexaenoic acid (DHA, 22:6n-3) have been reported to positively correlate with seizure thresholds in rodent seizure models. It is not known whether brain DHA depletion, achieved by chronic dietary omega-3 polyunsaturated fatty acid (PUFA) deficiency, lowers seizure thresholds in rats. Objective: The present study tested the hypothesis that lowering brain DHA concentration with chronic dietary n-3 PUFA deprivation in rats will reduce seizure thresholds, and that compared to injected oleic acid (OA), injected DHA will raise seizure thresholds in rats maintained on n-3 PUFA adequate and deficient diets. Methods: Rats (60 days old) were surgically implanted with electrodes in the amygdala, and subsequently randomized to the AIN-93G diet containing adequate levels of n-3 PUFA derived from soybean oil or an n-3 PUFA-deficient diet derived from coconut and safflower oil. The rats were maintained on the diets for 37 weeks. Afterdischarge seizure thresholds (ADTs) were measured every 4-6 weeks by electrically stimulating the amygdala. Between weeks 35 and 37, ADTs were assessed within 1 h of subcutaneous OA or DHA injection (600 mg/kg). Seizure thresholds were also measured in a parallel group of non-implanted rats subjected to the maximal pentylenetetrazol (PTZ, 110 mg/kg) seizure test. PUFA composition was measured in the pyriform-amygdala complex of another group of non-implanted rats sacrificed at 16 and 32 weeks. Results: Dietary n-3 PUFA deprivation did not significantly alter amygdaloid seizure thresholds or latency to PTZ-induced seizures. Acute injection of OA did not alter amygdaloid ADTs of rats on the n-3 PUFA adequate or deficient diets, whereas acute injection of DHA significantly increased amygdaloid ADTs in rats on the n-3 PUFA adequate control diet as compared to rats on the n-3 PUFA deficient diet (P < 0.05). Pyriform-amygdala DHA percent composition did not significantly differ between the groups, while n-6 docosapentaenoic acid, a marker of n-3 PUFA deficiency, was significantly increased by 2.9-fold at 32 weeks. Conclusion: Chronic dietary n-3 PUFA deficiency does not alter seizure thresholds in rats, but may prevent the anti-seizure effects of DHA.

Continuous multi-modality brain imaging reveals modified neurovascular seizure response after intervention.

We developed a multi-modal brain imaging system to investigate the relationship between blood flow, blood oxygenation/volume, intracellular calcium and electrographic activity during acute seizure-like events (SLEs), both before and after pharmacological intervention. Rising blood volume was highly specific to SLE-onset whereas blood flow was more correlated with all eletrographic activity. Intracellular calcium spiked between SLEs and at SLE-onset with oscillation during SLEs. Modified neurovascular and ionic SLE responses were observed after intervention and the interval between SLEs became shorter and more inconsistent. Comparison of artery and vein pulsatile flow suggest proximal interference and greater vascular leakage prior to intervention.

Imaging brain activity during seizures in freely behaving rats using a miniature multi-modal imaging system.

We report on a miniature label-free imaging system for monitoring brain blood flow and blood oxygenation changes in awake, freely behaving rats. The device, weighing 15 grams, enables imaging in a ∼ 2 × 2 mm field of view with 4.4 µm lateral resolution and 1 - 8 Hz temporal sampling rate. The imaging is performed through a chronically-implanted cranial window that remains optically clear between 2 to > 6 weeks after the craniotomy. This imaging method is well suited for longitudinal studies of chronic models of brain diseases and disorders. In this work, it is applied to monitoring neurovascular coupling during drug-induced absence-like seizures 6 weeks following the craniotomy.

Comparative study of five antiepileptic drugs on a translational cognitive measure in the rat: relationship to antiepileptic property.

RATIONALE: Antiepileptic drugs (AEDs) have been available for many years; yet, new members of this class continue to be identified and developed due to the limitations of existing drugs, which include a propensity for cognitive impairment. However, there is little preclinical information about the cognitive effects they produce, which clinically include deficits in attention and slowing of reaction time. OBJECTIVES: The purpose of this study was to profile two first-generation AEDs, phenytoin and valproate, and three second-generation AEDs, levetiracetam, pregabalin and lacosamide. Initially, each drug was examined across a range of well characterised preclinical seizure tests, and then each drug was evaluated in the five-choice serial reaction time test (5-CSRTT) based on efficacious doses from the seizure tests. MATERIALS AND METHODS: Each AED was tested for anti-seizure efficacy in either (1) the maximal electroshock seizure test, (2) s.c. PTZ seizure test, (3) amygdala-kindled seizures and (4) the genetic absence epilepsy rat of Strasbourg model of absence seizures. On completion of these studies, each drug was tested in rats trained to asymptotic performance in the 5-CSRTT (0.5 s SD, 5 s ITI, 100 trials). Male rats were used in all studies. RESULTS: Each AED was active in at least one of the seizure tests, although only valproate was active in each test. In the 5-CSRT test, all drugs with the exception of levetiracetam, significantly slowed reaction time and increased omissions. Variable effects were seen on accuracy. The effect on omissions was reversed by increasing stimulus duration from 0.5 to 5 s, supporting a drug-induced attention deficit. Levetiracetam had no negative effect on performance; indeed, reaction time was slightly increased (i.e. faster). CONCLUSIONS: These results highlight somewhat similar effects of phenytoin, valproate, pregabalin and lacosamide on attention and reaction time, and comparison to efficacious doses from the seizure tests support the view that there may be a better separation with the newer AEDs. Levetiracetam had no detrimental effect in the 5-CSRTT, which may be consistent with clinical experience where the drug is considered to be well tolerated amongst the AED class.