Background: Heavy metals such as lead are ubiquitous elements at exposure causing deleterious
effects on the brain and leading to neurodegenerative diseases. Aim: In this investigation, the
neurotherapeutic effects of ethanol extract of Curcuma longa (EECl) against lead‑induced hippocampal
neurotoxicity in rats were examined. Biochemical examination for antioxidant enzyme activity and
lipid peroxide level (malondialdehyde [MDA], superoxide dismutase [SOD], and glutathione [GSH])
was evaluated, the Barnes maze for learning and memory, and histological analysis (H and E stain)
for general histoarchitectural features to investigate the neurotherapeutic characteristics of EECl.
Materials and Methods: Six groups totalling 36 rats were created (n = 6). In the first group, rats
received distilled water (2 mg/kg), in the second, lead acetate (LA) (120 mg/kg), in the third, ascorbic
acid (100 mg/kg), and the 4th, 5th, and 6th groups, rats received LA (120 mg/kg) and EECl (375 mg/kg,
750 mg/kg, and 1500 mg/kg, respectively) for 14 days. Results: A significant learning and memory
deficit was seen in the LA‑treated group’s results, but a significant improvement was seen in the
EECl‑treated group. Increased oxidative stress was seen in the LA‑treated group, as evidenced by
an increase in MDA levels and a decrease in antioxidant enzymes (SOD and GSH). A decline in
MDA levels and an increase in SOD and GSH activity was the evidence of the ameliorative effects of
EECl treatment. Cytoarchitectural distortions relative to the control were observed with the LA‑treated
group. Mild distortion was however detected with EECl treatment. Conclusion: EECl has possible
neurotherapeutic properties against LA‑induced pathological changes in the hippocampus of Wistar
rats. EECl may have neuroprotective effects against degenerative alterations brought on by LA.

Background: Tramadol has a high potential for misuse resulting in cognitive impairment.
Zingiber officinale, however, possesses neuroprotective qualities. Objective: Microscopically
assessed hippocampal CA1 and CA3 following Z. officinale and tramadol treatment.
Materials and Methods: Two milliliters/kilogram of distilled water was given to Group 1,
Groups 2–5 were administered 50 mg/kg of tramadol while Group 3 was also administered 12.5 mg/
kg of naltrexone, and Groups 4 and 5 were also administered 500, and 1000 mg/kg ethanol extract of
Z. officinale (EEZO), respectively, orally for 21 days. The rats were euthanized and their brains were
collected, fixed in 10% formal saline, and processed routinely using crystal fast violet (CFV) stain for
the demonstration of Nissl substance, glial fibrillary acidic protein (GFAP) for the demonstration of
astrocytes, and Hematoxylin and Eosin for general histoarchitecture and estimation of cell number and
volume using physical dissector and Cavalieri estimator, respectively. Results: CFV stain revealed
alterations in regions of CA1 and CA3 of the hippocampus presenting as indistinct staining intensity
and peripheral Nissl substance accumulation in the tramadol‑treated group. GFAP revealed numerous
reactive astrocyte processes. The area of reactive astrocytes remarkably increased (P < 0.05) and
the intensity of the Nissl substance remarkably reduced in the tramadol-exposed group. When
compared to the control, the tramadol-exposed group’s hippocampal volume considerably (P < 0.05)
decreased (coefficient of error [CE] =0.050). The tramadol treatment group (CE = 0.090) relative to
the control group (CE = 0.060) showed a striking decrease (P < 0.05) in the number of pyramidal
cells in the CA3 region. The tramadol treatment group (CE = 0.090) compared to the control
group (CE = 0.060) showed a striking decrease (P < 0.05) in the number of pyramidal cells in the
CA3 region. Tramadol toxicity was attenuated in the groups treated with EEZO in a dose-dependent
manner. Conclusion: Z. officinale possesses a potential neuroprotective effect against tramadol‑induced
neurotoxicity.