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Cilostazol Ameliorates Motor Dysfunction and Schwann Cell Impairment in Streptozotocin-Induced Diabetic Rats
Lin-Li Chang1,2,3, Yu-Ming Wu2, Hung-Chen Wang4
1Department of Microbiology and Immunology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan.
Abstract:
This study investigated the effects of cilostazol on motor dysfunction, spinal motor neuron abnormalities, and schwannopathy in rats with diabetes. Diabetes mellitus (DM) was induced in rats via femoral intravenous streptozotocin (STZ) injection (60 mg/kg). After successful DM induction, cilostazol was administered on day 15 via oral gavage (100 mg/kg/day) for 6 weeks until sacrifice. Behavioral assays, including motor function, were performed weekly. The sciatic nerve, L5 spinal cord, and spinal ventral root were collected to evaluate the expression of the glial fibrillary acidic protein (GFAP), myelin protein zero (P0), and choline acetyltransferase (ChAT) by immunofluorescence and Western blotting. DM rats displayed decreased running speeds, running distances, and toe spread but increased foot pressure. In addition, loss of non-myelinating Schwann cells and myelin sheaths was observed in the sciatic nerve and L5 spinal ventral root. Reduced numbers of motor neurons were also found in the L5 spinal ventral horn. Cilostazol administration significantly potentiated running speed and distance; increased hind paw toe spread; and decreased foot pressure. In the sciatic nerve and L5 spinal ventral root, cilostazol treatment significantly improved non-myelinated Schwann cells and increased myelin mass. ChAT expression in motor neurons in the spinal ventral horn was improved, but not significantly. Cilostazol administration may protect sensorimotor function in diabetic rats.
Insights
Cilostazol improved motor function and nerve health in diabetic rats. The drug enhanced running ability and nerve cell integrity, suggesting a protective effect against diabetic neuropathy.
Area of Science:
- Neuroscience
- Pharmacology
- Diabetology
Background:
- Diabetes mellitus (DM) causes sensorimotor dysfunction and nerve damage.
- Diabetic neuropathy affects motor neurons and Schwann cells, leading to motor deficits.
- Current treatments for diabetic neuropathy are limited.
Purpose of the Study:
- To investigate the therapeutic effects of cilostazol on diabetic neuropathy in a rat model.
- To evaluate cilostazol's impact on motor function, spinal motor neurons, and peripheral nerve pathology.
- To assess cilostazol's influence on specific molecular markers related to nerve health.
Main Methods:
- Diabetes mellitus induced in rats using streptozotocin (STZ).
- Cilostazol administered orally for 6 weeks.
- Behavioral tests assessed motor function.
- Sciatic nerve, spinal cord, and ventral root tissues analyzed using immunofluorescence and Western blotting for GFAP, P0, and ChAT expression.
Main Results:
- Diabetic rats showed impaired motor function (reduced speed, distance, toe spread; increased foot pressure).
- Sciatic nerve and ventral root exhibited loss of Schwann cells and myelin.
- Cilostazol treatment significantly improved motor function and nerve myelination.
- Cilostazol increased non-myelinated Schwann cells and myelin mass in peripheral nerves.
Conclusions:
- Cilostazol demonstrates significant protective effects on sensorimotor function in diabetic rats.
- The drug ameliorates peripheral nerve damage, including Schwann cell loss and demyelination.
- Cilostazol may represent a potential therapeutic agent for diabetic neuropathy.
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