Effects of the Ca2+ antagonist nimodipine on functional deficits in the peripheral and central nervous system of streptozotocin-diabetic rats.
Diabetes mellitus can lead to functional and structural deficits in both the peripheral and central nervous system. The pathogenesis of these deficits is multifactorial, probably involving, among others, microvascular dysfunction and alterations in intracellular calcium homeostasis. The present study examined the effects of treatment with the Ca2+ antagonist nimodipine (20 mg/kg, intraperitoneal injection, every 48 h) on functional deficits in the peripheral and central nervous system in streptozotocin-diabetic rats. In a prevention experiment, treatment was initiated immediately after diabetes induction and continued for 10 weeks. In a reversal experiment, treatment was initiated 16 weeks after diabetes induction and continued for 12 weeks. Sciatic nerve motor and sensory conduction velocity, brainstem auditory-evoked potentials, and visual-evoked potentials were measured in control, untreated, and nimodipine-treated diabetic rats. In addition, long-term potentiation, a form of synaptic plasticity used as a model for learning and memory at the cellular level, was examined in hippocampal slices. Nimodipine treatment partially prevented deficits in nerve conduction velocity and hippocampal long-term potentiation in diabetic rats. However, nimodipine intervention treatment was unable to reverse established deficits in nerve conduction velocity, evoked potential latencies, or long-term potentiation. It is concluded that nimodipine can partially prevent early functional deficits in the peripheral and central nervous system of streptozotocin-diabetic rats but is unable to reverse late deficits.
Biessels
Geert Jan
GJ
Department of Medical Pharmacology of the Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, The Netherlands. g.j.biessels@neuro.azu.nl
ter Laak
Mariël P
MP
Kamal
Amer
A
Gispen
Willem Hendrik
WH
D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D001933:Brain Stem / Q000187:drug effects / Q000503:physiopathology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002490:Central Nervous System / Q000187:drug effects* / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000503:physiopathology*; D004334:Drug Administration Schedule; D004558:Electric Stimulation / Q000379:methods; D005074:Evoked Potentials, Visual / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects; D009553:Nimodipine / Q000494:pharmacology*; D017933:Peripheral Nervous System / Q000187:drug effects* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012584:Sciatic Nerve / Q000187:drug effects / Q000503:physiopathology; D013311:Streptozocin; D013997:Time Factors
D001786:Blood Glucose; D002121:Calcium Channel Blockers; D009553:Nimodipine; D013311:Streptozocin