Stereological evaluation of the neuroprotective effects of curcumin on the spinal cord in a streptozotocin-induced diabetic rat model.

Abstract

Introduction: This study examined how curcumin influences spinal cord morphological parameters in rats with STZ-induced diabetes using unbiased stereological methods.

Methods: Fifty-six female Wistar albino rats were randomly divided into seven experimental groups (n = 8): Control, Sham, Curcumin, Diabetes Mellitus (DM), DM + Curcumin after 7 days (DC1), DM + Curcumin after 21 days (DC2), and DM + Curcumin simultaneously (DC3). Diabetes was induced via a single intraperitoneal dose of STZ (50 mg/kg). Curcumin was administered at a dose of 30 mg/kg via intragastric gavage for 14 consecutive days. C3-C5 spinal segments were collected at the end of the experiment, processed for histology, and stained with toluidine blue and cresyl violet for stereological analysis. Neuronal quantification in the anterior horn was performed using physical fractionator. The volume fractions of the spinal cord, including white matter (WM/total volume) and gray matter (GM/total volume), were estimated using the Cavalieri's principle.

Results: The diabetic (DM) group showed a significant reduction in motor neuron number compared with the Control group (p = 0.019), demonstrating diabetes-induced neuronal loss. In contrast, the DC2 treatment group showed a significant increase in motor neuron counts compared with DM (p = 0.04), suggesting a possible neuroprotective effect of curcumin. Total spinal cord volume did not differ significantly among groups. WM/Total ratio decreased in the Sham group but increased with curcumin (DC3). GM/Total ratio was lower in DC3 than Sham, and curcumin produced a non-significant improvement compared with diabetic rats. Increased caspase-3 immunoreactivity in the diabetic group indicates activation of apoptotic pathways, consistent with the observed reduction in motor neuron number and soma size. Furthermore, the marked increase in GFAP immunoreactivity, particularly in the DC2 group, reflects astrocyte activation and a reactive gliosis, which are commonly associated with metabolic stress and neuroinflammation in diabetic conditions.

Discussion: Curcumin administration partially mitigated spinal motor neuron loss induced by experimental diabetes. The timing of curcumin treatment influenced its efficacy. These findings suggest that curcumin may have therapeutic potential for preventing diabetes-induced spinal cord neurodegeneration.