Change in the central control of the bladder function of rats with focal cerebral infarction induced by photochemically-induced thrombosis.

Yuya Ota,Nayuka Matsuyama,Taiki Kato,Yasue Kubota,Mami Matsumoto,Tomoya Kataoka,Yuji Hotta,Kazunori Kimura,Takahiro Yasui,Kazunobu Sawamoto,Takashi Hamakawa

doi:10.1371/journal.pone.0255200

Abstract

The photochemically-induced thrombosis (photothrombosis) method can create focal cerebral infarcts anywhere in the relatively superficial layers of the cerebrum; it is easy to implement and minimally invasive. Taking advantage of this versatility, we aimed to establish a new rat model of urinary frequency with focal cerebral infarction, which was characterized by its simplicity, nonlethal nature, and high reproducibility. The prefrontal cortex and the anterior cingulate cortex, which are involved in lower urinary tract control, were targeted for focal cerebral infarction, and urinary parameters were measured by cystometrogram. Cystometric analysis indicated that micturition intervals significantly shortened in photothrombosis-treated rats compared with those in the sham operative group on Days 1 and 7 (P < 0.01), but prolonged after 14 days, with no difference between the two groups. Immunopathological evaluation showed an accumulation of activated microglia, followed by an increase in reactive astrocytes at the peri-infarct zone after photothrombotic stroke. Throughout this study, all postphotothrombosis rats showed cerebral infarction in the prefrontal cortex and anterior cingulate cortex; there were no cases of rats with fatal cerebral infarction. This model corresponded to the clinical presentation, in that the micturition status changed after stroke. In conclusion, this novel model combining nonlethality and high reproducibility may be a suitable model of urinary frequency after focal cerebral infarction.

Highlights

Cerebral infarction is associated with a high incidence of lower urinary tract symptoms (LUTS), urinary bladder overactivity, which reduces a patient’s quality of life [1,2]
Our aim was to establish a new rat model of urinary frequency, with focal cerebral infarction in prefrontal cortex (PFC) and anterior cingulate cortex (ACC) induced by photothrombosis, which is easy to perform and minimally invasive, and to observe histopathological changes in the brain
No damage was observed in the brain stem, such as the periaqueductal gray (PAG) or pontine micturition center (PMC) regions, in either group

Summary

Introduction

Cerebral infarction is associated with a high incidence of lower urinary tract symptoms (LUTS), urinary bladder overactivity, which reduces a patient’s quality of life [1,2]. There is no established LUTS treatment that targets the central nervous system. We believe that one of the reasons for the lack of development of treatments for the central nervous system is the lack of animal models. Middle cerebral artery occlusion (MCAO) rats have generally been used as a model for bladder overactivity caused by cerebral infarction [5,6]. They have the disadvantages of variability in the infarct volume and a high mortality rate due to the large infarct area and local traumatic effect [5,7,8]. Creating an MCAO rat model is surgically demanding [9]

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Conclusion