Maternal treatment with oral intestinal alkaline phosphatase mitigates high fat diet-induced cognitive disorders in offspring mice.

Intestinal alkaline phosphatase (IAP) is an endogenous enzyme that promotes gastrointestinal homeostasis by detoxifying inflammatory mediators, tightening the gut barrier and promoting a healthy microbiome. Oral IAP administration was efficacious in ameliorating diabetes in a high fat diet (HFD)-induced murine model. In humans, maternal obesity and diabetes during pregnancy have been associated with an increased risk of autism spectrum disorders (ASD).

Poly-Arginine Peptides R18 and R18D Improve Functional Outcomes After Endothelin-1-Induced Stroke in the Sprague Dawley Rat.

We have previously demonstrated that R18 and its d-enantiomer, R18D, are neuroprotective at 24 hours following intraluminal filament occlusion of the middle cerebral artery (MCAO) in the rat. This study examined R18 and R18D effectiveness in improving functional outcomes at up to 56 days poststroke following endothelin-1-induced MCAO. Peptides were administered intravenously at doses of 100, 300, or 1000 nmol/kg, 60 minutes after MCAO.

Selective reductions in subpopulations of GABAergic neurons in a developmental rat model of epilepsy.

In the rat, early postnatal development is a critical period for neuronal migration, differentiation and network formation, requiring appropriate and timely glutamate and gamma-aminobutyric acid (GABA) signaling. Insults that affect either of these systems may result in increased excitatory activity, potentially leading to changes in neuronal proliferation and/or connectivity. We have previously shown that postnatal administration of low doses of domoic acid (DOM) can produce many of the behavioral and morphological changes found in current animal models of temporal lobe epilepsy (TLE), as well as the human condition.

Hippocampal mossy fiber sprouting and elevated trkB receptor expression following systemic administration of low dose domoic acid during neonatal development.

We have previously reported that serial systemic injections of low-dose (subconvulsive) domoic acid (DOM) during early postnatal development produces changes in both behavior and hippocampal cytoarchitecture in aged rats (17 months) that are similar to those seen in existing animal models of temporal lobe epilepsy. Herein we report further hippocampal changes, consisting of mossy fiber sprouting and associated changes in the trkB receptor population in young adult (3 months) rats, and further, report that these changes show regional variation throughout the septo-temporal axis of the hippocampus. Groups of Sprague Dawley rat pups were injected daily from postnatal day 8-14 with either saline (n = 23) or 20 microg/kg DOM (n = 25), tested for key indicators of neonatal neurobehavioral development, and then left undisturbed until approximately 90 days of age, at which time brain tissue was removed, hippocampi were dissected, fixed and processed using either Timm's stain to visualize hippocampal mossy fiber sprouting (MFS) or trkB immunohistochemistry to visualize full length trkB receptors.

An improved post-operative care protocol allows detection of long-term functional deficits following MCAo surgery in rats.

Developing new therapeutants for stroke requires animal models in which typical stroke outcomes can be detected. In rats, temporary occlusion of the middle cerebral artery (MCAo) closely resembles reversible human ischemic stroke, but most neuroprotection studies have used limited, short-term (1-2 weeks) behavioural and histological endpoints in this model. Further, the use of this model for assessing long-term recovery has been questioned.