Effects of the Ca2+ antagonist nimodipine on functional deficits in the peripheral and central nervous system of streptozotocin-diabetic rats

Biessels, Geert Jan; Laak, Mariël P. ter; Kamal, Amer; Gispen, Willem Hendrik

doi:10.1016/j.brainres.2004.12.025

Cited by 26 publications

(16 citation statements)

References 31 publications

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“…In the present study, DH exaggerated neuronal loss in lithium-pilocarpine-induced SE. In addition to SE-related excitotoxicity (Curia et al 2008), DH plus SE may amplify the adverse effects of hyperglycemia on neurons, both the direct effects and the indirect effects, such as diabetic oxidative stress (Zupan et al 2008), microvascular changes (Mraovitch et al 2005;Qiu et al 2008), and altered calcium homeostasis (Raza et al 2004;Biessels et al 2005). As neuronal glucose uptake depends on the extracellular concentration of glucose, cellular damage can ensue after persistent episodes of hyperglycemia (Tomlinson and Gardiner 2008).…”

Section: Discussionmentioning

confidence: 98%

Diabetic Hyperglycemia Aggravates Seizures and Status Epilepticus-induced Hippocampal Damage

et al. 2009

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Epileptic seizures in diabetic hyperglycemia (DH) are not uncommon. This study aimed to determine the acute behavioral, pathological, and electrophysiological effects of status epilepticus (SE) on diabetic animals. Adult male Sprague-Dawley rats were first divided into groups with and without streptozotocin (STZ)-induced diabetes, and then into treatment groups given a normal saline (NS) (STZ-only and NS-only) or a lithium-pilocarpine injection to induce status epilepticus (STZ + SE and NS + SE). Seizure susceptibility, severity, and mortality were evaluated. Serial Morris water maze test and hippocampal histopathology results were examined before and 24 h after SE. Tetanic stimulation-induced long-term potentiation (LTP) in a hippocampal slice was recorded in a multi-electrode dish system. We also used a simulation model to evaluate intracellular adenosine triphosphate (ATP) and neuroexcitability. The STZ + SE group had a significantly higher percentage of severe seizures and SE-related death and worse learning and memory performances than the other three groups 24 h after SE. The STZ + SE group, and then the NS + SE group, showed the most severe neuronal loss and mossy fiber sprouting in the hippocampal CA3 area. In addition, LTP was markedly attenuated in the STZ + SE group, and then the NS + SE group. In the simulation, increased intracellular ATP concentration promoted action potential firing. This finding that rats with DH had more brain damage after SE than rats without diabetes suggests the importance of intensively treating hyperglycemia and seizures in diabetic patients with epilepsy.

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Section: Discussionmentioning

confidence: 98%

Diabetic Hyperglycemia Aggravates Seizures and Status Epilepticus-induced Hippocampal Damage

et al. 2009

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“…There have been promising effects of drugs that target glucocorticoids (Stranahan et al, 2010), GLP-1 (Gault et al, 2010; Iwai et al, 2009), glucose-dependent insulinotropic polypeptide (Porter et al, 2011), and glucose control (Izumi et al, 2003). Initiation of treatment shortly after diabetes induction with enalapril, an angiotensin-converting enzyme inhibitor, and nimodipine, a calcium channel blocker, prevented diabetes-induced alterations in LTP but delayed treatment was not able to reverse already existing hippocampal damage (Biessels et al, 2005; Manschot et al, 2003). The results of these studies imply that there may be a window of opportunity to reverse neurobehavioral complications from diabetes.…”

Section: Experimental Diabetes and Other Forms Of Hippocampal Neurmentioning

confidence: 99%

Effects of diabetes on hippocampal neurogenesis: Links to cognition and depression

Sommers

Lucki

2013

Neuroscience & Biobehavioral Reviews

220

160

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Diabetes often leads to a number of complications involving brain function, including cognitive decline and depression. In addition, depression is a risk factor for developing diabetes. A loss of hippocampal neuroplasticity, which impairs the ability of the brain to adapt and reorganize key behavioral and emotional functions, provides a framework for understanding this reciprocal relationship. The effects of diabetes on brain and behavioral functions in experimental models of type 1 and type 2 diabetes are reviewed, with a focus on the negative impact of impaired hippocampal neurogenesis, dendritic remodeling and increased apoptosis. Mechanisms shown to regulate neuroplasticity and behavior in diabetes models, including stress hormones, neurotransmitters, neurotrophins, inflammation and aging, are integrated within this framework. Pathological changes in hippocampal function can contribute to the brain symptoms of diabetes-associated complications by failing to regulate the hypothalamic-pituitary-axis, maintain learning and memory and govern emotional expression. Further characterization of alterations in neuroplasticity along with glycemic control will facilitate the development and evaluation of pharmacological interventions that could successfully prevent and/or reverse the detrimental effects of diabetes on brain and behavior.

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“…It has been reported that nimodipine ameliorates existing experimental diabetic neuropathy in diabetic rats (Kappelle et al, 1993). Nimodipine treatment improves Ca 2+ -dependent forms of synaptic plasticity in the hippocampus of diabetic rats (Biessels et al, 2002), partially prevents deficits in nerve conduction velocity and hippocampal long-term potentiation (Biessels et al, 2005). Recent results indicate that nimodipine can improve experimental diabetic neuropathy through a vascular mechanism, possibly in combination with direct neuronal effects (Biessels et al, 2002).…”

Section: Introductionmentioning

confidence: 97%

The Effect of Nimodipine on Calcium Homeostasis and Pain Sensitivity in Diabetic Rats

et al. 2006

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1. The pathogenesis of diabetic neuropathy is a complex phenomenon, the mechanisms of which are not fully understood. Our previous studies have shown that the intracellular calcium signaling is impaired in primary and secondary nociceptive neurons in rats with streptozotocin (STZ)-induced diabetes. Here, we investigated the effect of prolonged treatment with the L-type calcium channel blocker nimodipine on diabetes-induced changes in neuronal calcium signaling and pain sensitivity. 2. Diabetes was induced in young rats (21 p.d.) by a streptozotocin injection. After 3 weeks of diabetes development, the rats were treated with nimodipine for another 3 weeks. The effect of nimodipine treatment on calcium homeostasis in nociceptive dorsal root ganglion neurons (DRG) and substantia gelatinosa (SG) neurons of the spinal cord slices was examined with fluorescent imaging technique. 3. Nimodipine treatment was not able to normalize elevated resting intracellular calcium ([Ca(2+)]( i )) levels in small DRG neurons. However, it was able to restore impaired Ca(2+) release from the ER, induced by either activation of ryanodine receptors or by receptor-independent mechanism in both DRG and SG neurons. 4. The beneficiary effects of nimodipine treatment on [Ca(2+)]( i ) signaling were paralleled with the reversal of diabetes-induced thermal hypoalgesia and normalization of the acute phase of the response to formalin injection. Nimodipine treatment was also able to shorten the duration of the tonic phase of formalin response to the control values. 5. To separate vasodilating effect of nimodipine Biessels et al., (Brain Res. 1035:86-93) from its effect on neuronal Ca(2+) channels, a group of STZ-diabetic rats was treated with vasodilator - enalapril. Enalapril treatment also have some beneficial effect on normalizing Ca(2+) release from the ER, however, it was far less explicit than the normalizing effect of nimodipine. Effect of enalapril treatment on nociceptive behavioral responses was also much less pronounced. It partially reversed diabetes-induced thermal hypoalgesia, but did not change the characteristics of the response to formalin injection. 6. The results of this study suggest that chronic nimodipine treatment may be effective in restoring diabetes-impaired neuronal calcium homeostasis as well as reduction of diabetes-induced thermal hypoalgesia and noxious stimuli responses. The nimodipine effect is mediated through a direct neuronal action combined with some vascular mechanism.

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Effects of the Ca2+ antagonist nimodipine on functional deficits in the peripheral and central nervous system of streptozotocin-diabetic rats

Cited by 26 publications

References 31 publications

Diabetic Hyperglycemia Aggravates Seizures and Status Epilepticus-induced Hippocampal Damage

Diabetic Hyperglycemia Aggravates Seizures and Status Epilepticus-induced Hippocampal Damage

Effects of diabetes on hippocampal neurogenesis: Links to cognition and depression

The Effect of Nimodipine on Calcium Homeostasis and Pain Sensitivity in Diabetic Rats

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