Amazon rainforest rodents (Proechimys) are resistant to post-stroke epilepsy.

There are no clinical interventions to prevent post-injury epilepsy, a common and devastating outcome after brain insults. Epileptogenic events that run from brain injury to epilepsy are poorly understood. Previous studies in our laboratory suggested Proechimys, an exotic Amazonian rodent, as resistant to acquired epilepsy development in post-status epilepticus models. The present comparative study was conducted to assess (1) stroke-related brain responses 24-h and 30 days after cortical photothrombosis and (2) post-stroke epilepsy between Proechimys rodents and Wistar rats, a traditional animal used for laboratory research. Proechimys group showed smaller volume of ischemic infarction and lesser glial activation than Wistar group. In contrast to Wistar rats, post-stroke decreased levels of pro-inflammatory cytokines and increased levels of anti-inflammatory mediators and growth factors were found in Proechimys. Electrophysiological signaling changes assessed by cortical spreading depression, in vitro and in vivo, showed that Wistar's brain is most severely affected by stroke. Chronic electrocorticographic recordings showed that injury did not lead to epilepsy in Proechimys whereas 88% of the Wistar rats developed post-stroke epilepsy. Science gains insights from comparative studies on diverse species. Proechimys rodents proved to be a useful animal model to study antiepileptogenic mechanisms after brain insults and complement conventional animal models.

Transcranial low-level laser therapy in an in vivo model of stroke: Relevance to the brain infarct, microglia activation and neuroinflammation.

Stroke is the main cause of death and functional disability. The available therapy affects only 5% of patients, and new therapeutic approaches have been constantly tested. Transcranial photobiomodulation (PBM) is promising for its neuroprotective effect on brain injuries. Thus, the present study investigated the PBM effects in an in vivo model of ischemic stroke induced by photothrombosis (PT). Five different groups of Wistar rats were submitted or not to a daily dose of fish oil or/and laser sessions for 2 months. The ischemia volume was evaluated by stereology; GFAP, Iba and NeuN by immunohistochemistry; TNF-α, IL-1ß, IL-6, IL-10 and TGF-ß by ELISA assay. PBM influenced both the lesion volume and the GFAP. Furthermore, PBM and Ω-3 or both reduced Iba RNAm. PBM reduced TNF-α, IL-1ß, IL-6, brain damage, neuroinflammation and microglial activation, and it increased astroglial activity in peri-lesioned region after stroke.

Repetitive transcranial photobiomodulation but not long-term omega-3 intake reduces epileptiform discharges in rats with stroke-induced epilepsy.

Epilepsy is a yet under-recognized consequence after a stroke and nearly 30% of cases are pharmacoresistant. There is an unmet need for therapeutic interventions during epileptogenesis for better long-term disease outcomes. Transcranial photobiomodulation (PBM) and omega-3 (Ω-3) dietary supplementation are two approaches that have been shown promising neuroprotective effects after brain injuries. Here, we studied the PBM treatment or Ω-3 diet during epileptogenesis in long-term recurrent spontaneous abnormal electrical discharges after stroke. Wistar rats received repetitive 780 nm-laser in the scalp or oral diet with Ω-3 for 2-months after photothrombotic stroke. EEG recordings were performed 60 days after treatment end. PBM but not Ω-3 reduced both electrographic seizure duration and spikes number in the ipsilateral and contralateral cortices and ventral posteromedial thalamic nucleus. Conclusively, PBM reduced epileptiform discharges in stroke-induced epilepsy. Our results suggest the PBM as a therapeutic approach for stroke-induced epileptogenesis to minimize long-term disease outcomes.

Robust Network Inhibition and Decay of Early-Phase LTP in the Hippocampal CA1 Subfield of the Amazon Rodent Proechimys.

Background: Diverse forms of long-term potentiation (LTP) have been described, but one of the most investigated is encountered in the glutamatergic synapses of the hippocampal cornu Ammonis (CA1) subfield. However, little is known about synaptic plasticity in wildlife populations. Laboratory animals are extremely inbred populations that have been disconnected from their natural environment and so their essential ecological aspects are entirely absent. Proechimys are small rodents from Brazil's Amazon rainforest and their nervous systems have evolved to carry out specific tasks of their unique ecological environment. It has also been shown that long-term memory duration did not persist for 24-h in Proechimys, in contrast to Wistar rats, when both animal species were assessed by the plus-maze discrimination avoidance task and object recognition test. Methods: In this work, different protocols, such as theta burst, single tetanic burst or multiple trains of high frequency stimulation (HFS), were used to induce LTP in hippocampal brain slices of Proechimys and Wistar rats. Results: A protocol-independent fast decay of early-phase LTP at glutamatergic synapses of the CA1 subfield was encountered in Proechimys. Long-term depression (LTD) and baseline paired-pulse facilitation (PPF) were investigated but no differences were found between animal species. Input/output (I/O) relationships suggested lower excitability in Proechimys in comparison to Wistar rats. Bath application of d-(-)-2-amino-5-phosphonopentanoicacid (D-AP5) and CNQX prevented the induction of LTP in both Proechimys and Wistar. However, in marked contrast to Wistar rats, LTP induction was not facilitated by the GABAA antagonist in the Amazon rodents, even higher concentrations failed to facilitate LTP in Proechimys. Next, the effects of GABAA inhibition on spontaneous activity as well as evoked field potentials (FPs) were evaluated in CA1 pyramidal cells. Likewise, much lower activity was detected in Proechimys brain slices in comparison to those of the Wistar rats. Conclusions: These findings suggest a possible high inhibitory tone in the CA1 network mediated by GABAA receptors in the Amazon rodents. Currently, neuroscience research still seeks to reveal molecular pathways that control learning and memory processes, Proechimys may prove useful in identifying such mechanisms in complement to traditional animal models.

Different patterns of epileptiform-like activity are generated in the sclerotic hippocampus from patients with drug-resistant temporal lobe epilepsy.

Human hippocampal slice preparations from patients with temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS) are excellent material for the characterization of epileptiform-like activity. However, it is still unknown if hippocampal regions as cornu Ammonis (CA) 1, CA3 and CA4, generate population epileptiform-like activity. Here, we investigated epileptiform activities of the subiculum, CA1, CA2, CA3, CA4 (induced by elevation of extracellular potassium concentration) and the dentate gyrus (induced with hilar stimulation and elevation of potassium concentration) from sclerotic hippocampi of patients with drug-resistant TLE. Five types of epileptiform-like activity were observed: interictal-like events; periodic ictal spiking; seizure-like events; spreading depression-like events; tonic seizure-like events and no activity. Different susceptibilities to generate epileptiform activity among hippocampal regions were observed; the dentate gyrus was the most susceptible region followed by the subiculum, CA4, CA1, CA2 and CA3. The incidence of epileptiform activity pattern was associated with specific regions of the hippocampal formation. Moreover, it was observed that each region of the hippocampal formation exhibits frequency-specific ranges in each subfield of the sclerotic human tissue. In conclusion, this study demonstrates that epileptiform-like activity may be induced in different regions of the hippocampal formation, including regions that are severely affected by neuronal loss.