Biomedical subjects

Geert Jan Biessels

Publications and source records attributed to Geert Jan Biessels.

3 recordsLinked to original sources

PubMed2003

Angiotensin converting enzyme inhibition partially prevents deficits in water maze performance, hippocampal synaptic plasticity and cerebral blood flow in streptozotocin-diabetic rats.

Vascular dysfunction is important in the pathogenesis of peripheral complications of diabetes. However, the effects of diabetes on cerebral blood flow and the role of vascular deficits in the pathogenesis of diabetic encephalopathy are still unknown. The present study examined whether experimental diabetes is associated with reduced cerebral blood flow and whether treatment with enalapril can improve cerebral perfusion and function (blood flow and functional cerebral deficits). Streptozotocin-diabetic rats were treated with the ACE inhibitor enalapril (24 mg/kg) from onset of diabetes. After 14 weeks of diabetes, 12 enalapril treated and 12 untreated diabetic rats, and 12 nondiabetic age-matched control rats were tested in a spatial version of the Morris water maze. After 16 weeks of diabetes, in the same groups, blood flow in the hippocampus and thalamus was measured by hydrogen clearance microelectrode polarography. In a separate study, hippocampal long-term potentiation was measured after 26 weeks of diabetes. Water maze performance and hippocampal long-term potentiation were impaired in diabetic rats. Furthermore, blood flow in diabetic rats was reduced by 30% (P<0.001) in the hippocampus and by 37% (P<0.005) in the thalamus compared to nondiabetic controls. Enalapril treatment significantly improved water maze performance (P<0.05), hippocampal long term potentiation (P<0.05) and hippocampal blood flow (P<0.05). Cerebral perfusion is reduced in diabetic rats compared to controls. Treatment aimed at the vasculature can improve cerebral blood flow, deficits in Morris maze performance and long term potentiation. These findings suggest that vasculopathy plays a role in the development of cerebral dysfunction in diabetic rats.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2002

Neuronal Ca2+ disregulation in diabetes mellitus.

The Ca(2+) hypothesis of brain ageing and dementia may account for part of the available data on the pathogenesis of dementia and certain neurodegenerative disorders. The hypothesis proposes that disturbances in the homeostasis of neuronal cytosolic free Ca(2+) are part of a final common pathway, ultimately leading to neuronal dysfunction and cell death. The hypothesis also proposes that a small change in cytosolic free Ca(2+) sustained over a long period of time will result in similar damage as a large change over a short period. Diabetes mellitus is associated with neurological complications in the peripheral and central nervous system, as reflected in peripheral neuropathy, modest cognitive impairments and an increased risk of dementia. In animal models of diabetes, learning impairments are associated with alterations in Ca(2+) -dependent forms of hippocampal synaptic plasticity. Disturbances in the homeostasis of cytosolic free Ca(2+) may present a final common pathway in the multifactorial pathogenesis of neurological complications of diabetes, which involves vascular changes, oxidative stress, and non-enzymatic protein glycation. In line with the Ca(2+) hypothesis of neurodegenerative disorders, a prolonged, small increase in basal cytosolic Ca(2+) levels indeed exists in sensory neurones of diabetic animals. In addition, Ca(2+) dynamics are affected. Ca(2+) channel blockers, such as nimodipine, have been shown to improve experimental peripheral neuropathy, through a vascular mechanism, possibly in combination with direct neuronal effects. Preliminary studies indicate that nimodipine may also improve Ca(2+)-dependent forms of synaptic plasticity in the hippocampus of diabetic rats.

Aging↗

PubMed2002

Ageing and diabetes: implications for brain function.

Diabetes mellitus is associated with moderate cognitive deficits and neurophysiological and structural changes in the brain, a condition that may be referred to as diabetic encephalopathy. Diabetes increases the risk of dementia, particularly in the elderly. The emerging view is that the diabetic brain features many symptoms that are best described as "accelerated brain ageing." The clinical characteristics of diabetic encephalopathy are discussed, as well as behavioural (e.g. spatial learning) and neurophysiological (e.g. hippocampal synaptic plasticity) findings in animal models. Animal models can make a substantial contribution to our understanding of the pathogenesis, which shares many features with the mechanisms underlying brain ageing. By unravelling the pathogenesis, targets for pharmacotherapy can be identified. This may allow treatment or prevention of this diabetic complication in the future. We discuss changes in glutamate receptor subtypes, in second-messenger systems and in protein kinases that may account for the alterations in synaptic plasticity. In addition, the possible role of cerebrovascular changes, oxidative stress, nonenzymatic protein glycation, insulin and alterations in neuronal calcium homeostasis are addressed.

Aging↗