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How does cisplatin scramble rat hippocampal memory circuits?

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Cisplatin cut survival, impaired recognition memory, and ramped hippocampal inflammation, oxidative stress, and glutamate-receptor mRNA.

Source

Cisplatin induces hippocampal neurotoxicity and cognitive impairment in rats through neuroinflammation, oxidative stress, and overexpression of glutamatergic receptors mRNA

Alhowail AH · Frontiers in pharmacology · 2025

doi.org/10.3389/fphar.2025.1592511Read the full paper ↗21 citationscc by

Study at a glance

Design
Animal / in-vitro — Male Wistar rats randomized to control vs cisplatin (8 mg/kg i.p. ×3) with survival, YMT/NORT, and hippocampal inflammatory/oxidative/glutamatergic assays
N
N=20 · 10 control + 10 cisplatin; some assays report n=6 survivors/completers
Population
Eight-week-old male Wistar rats
Outcome
Survival, body weight, memory behavior, and hippocampal inflammation/oxidative/glutamatergic markers

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What they did

Twenty rats were split into control vs cisplatin (8 mg/kg i.p. every 2 days ×3). Investigators tracked survival/weight, ran Y-maze and novel-object tests, then assayed hippocampal cytokines, ROS/antioxidant markers, mitochondrial complex I, lipid peroxidation, and AMPAR/NMDAR mRNA.

What they found

Survival fell to 40%, weight dropped, NORT exploration declined, and NF-κB/TNF-α/IL-6 rose with oxidative stress and glutamatergic receptor overexpression—supporting a neuroinflammation–glutamate mechanism for chemo-brain.

The limits

What it doesn't show

Not a human cognitive trial; high experimental dosing and mortality limit direct clinical dose translation.

Key terms

Chemo-brain
Chemotherapy-associated cognitive impairment, here modeled after cisplatin.
Y-maze / NORT
Behavioral tests of spatial/recognition memory in rodents.
NF-κB / TNF-α / IL-6
Pro-inflammatory mediators elevated in cisplatin hippocampi.
AMPAR / NMDAR
Ionotropic glutamate receptors whose hippocampal expression was assessed.
Mitochondrial complex I (MCI)
Respiratory-chain activity that declined with cisplatin.

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What is the study’s primary design?

Common questions

Was this done in patients?

No—male Wistar rats only.

What dose was used?

8 mg/kg intraperitoneally every 2 days for three cycles.

Did cognition change?

Yes—novel-object exploration fell; Y-maze entries into the novel arm also declined.

Proposed mechanism?

Hippocampal neuroinflammation plus glutamatergic receptor overactivation with oxidative stress.

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