Abstract:
Ciprofloxacin (CPFX), a broad-spectrum antibiotic in the fluoroquinolone class, is one
of the most widely prescribed agents for uncomplicated cases of urinary tract infections
(UTI). However, over the past decade, the safety of CPFX was questioned due to
reported cases regarding its adverse side effects on the nervous system.
Hence, our aim is to test the effect of CPFX on cognition, hippocampal neurogenesis,
and pain sensitivity in healthy one-month old male Sprague-Dawley rats.
One-month old male Sprague-Dawley rats were randomly and equally divided into two
groups: control (vehicle) and ciprofloxacin-treated (44mg/kg, orally for 14 days) rats. A
battery of cognitive and sensory behavioral tests (sequential learning, T-maze, Y-maze,
novel-object recognition, mechanical and thermal sensitivity tests) were conducted
before, and weekly for two weeks after treatment. The rats also received 3 injections of
BrDU (200mg/kg) where the total dosage was equally distributed over the first three
days of treatment to label proliferating cells and immature neurons in the subgranular
zone (SGZ) of the dendate gyrus (DG) of the hippocampus. At the end of the
experiment, fixed brain tissue were collected and processed for immunofluorescence
staining using BrDU and NeuN as neuronal markers for neurogenesis. The data was
analyzed and plotted using Graphpad prism.
Our data has shown that CPFX did not impair cognitive functions such as episodic,
recognition, reference, and spatial-working memories. This was consistent with the
immunofluorescence staining which demonstrated that CPFX did not alter hippocampal
neurogenesis. However, CPFX affected the peripheral nervous system (PNS) by
decreasing the sensitivity threshold to thermal and mechanical stimuli over time.
The mechanism underlying the development of pain in the CPFX-treated group is not
fully understood and requires further investigations. We speculate that CPFX may have
triggered a pain-related behavior by inducing a hyper-excitable state in the dorsal horn
of the spinal cord through inhibition of GABAergic interneurons.
