The Autophagic and Apoptotic Death of Forebrain Neurons of Rats with Global Brain Ischemia Is Diminished by the Intranasal Administration of Insulin: Possible Mechanism of Its Action.

Insulin is a promising neuroprotector. To better understand the mechanism of insulin action, it was important to show its ability to diminish autophagic neuronal death in animals with brain ischemic and reperfusion injury. In forebrain ischemia and reperfusion, the number of live neurons in the hippocampal CA1 region and frontal cortex of rats decreased to a large extent.

The Effect of Intranasal Administration of Gangliosides on the Viability of CA1 Hippocampal Neurons in Rat Two-Vessel Occlusion Model of Forebrain Ischemia/Reperfusion Injury.

Intranasal administration of total bovine brain gangliosides (6 mg/kg) to rats protected the CA1 hippocampal neurons from the death caused by two-vessel occlusion model (with hypotension) of forebrain ischemia/reperfusion injury. The immunohistochemical reaction of specific antibodies to marker proteins of activated microglia (Iba1) and astrocytes (GFAP) in hippocampal slices revealed the neuroprotective effect of exogenous gangliosides which can be mostly explained by their ability to suppress neuroinflammation and gliosis. The expression of neurotrophic factor BDNF in the CA1 region of hippocampus did not differ in sham-operated rats and animals exposed to ischemia/reperfusion.

Prospects for the Use of Intranasally Administered Insulin and Insulin-Like Growth Factor-1 in Cerebral Ischemia.

Current approaches to the treatment of stroke have significant limitations, and neuroprotective therapy is ineffective. In view of this, searching for effective neuroprotectors and developing new neuroprotective strategies remain a pressing topic in research of cerebral ischemia. Insulin and insulin-like growth factor-1 (IGF-1) play a key role in the brain functioning by regulating the growth, differentiation, and survival of neurons, neuronal plasticity, food intake, peripheral metabolism, and endocrine functions.

Insulin and α-Tocopherol Enhance the Protective Effect of Each Other on Brain Cortical Neurons under Oxidative Stress Conditions and in Rat Two-Vessel Forebrain Ischemia/Reperfusion Injury.

Clinical trials show that insulin administered intranasally is a promising drug to treat neurodegenerative diseases, but at high doses its use may result in cerebral insulin resistance. Identifying compounds which could enhance the protective effects of insulin, may be helpful to reduce its effective dose. Our aim was thus to study the efficiency of combined use of insulin and α-tocopherol (α-T) to increase the viability of cultured cortical neurons under oxidative stress conditions and to normalize the metabolic disturbances caused by free radical reaction activation in brain cortex of rats with two-vessel forebrain ischemia/reperfusion injury.

Intranasal Administration of Insulin and Gangliosides Improves Spatial Memory in Rats with Neonatal Type 2 Diabetes Mellitus.

We analyzed the effects of intranasal administration of insulin (0.48 U/rat) and gangliosides (6 mg/kg) on spatial memory in rats with the neonatal model of the type 2 diabetes mellitus. The development of diabetes was verified by the glucose tolerance test.