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Purpose <p>This study aimed to elucidate the pathophysiology of overactive bladder (OAB) associated with vesical adaptation response to diuresis (VARD), the homeostatic system adjusting bladder volume in response to diuresis, by identifying regulatory mechanisms for VARD in the brain.</p> Methods <p>Male 14-week-old Sprague–Dawley rats underwent cystometry with saline infused into the bladder at rates of 0 mL/h (Sham group), 1 mL/h (Low-rate group), or 10 mL/h (High-rate group). Neural activity in the prefrontal cortex (PFC) and periaqueductal gray (PAG) was assessed in each group using c-Fos staining. Effects of ibotenic acid (IBO) destruction of PFC or PAG lesions on VARD were compared using metabolic cage studies and cystometry, assuming that rates of bladder infusion and vesical filling were equal. Control groups received phosphate-buffered saline injections into the PFC or PAG (PBS-PFC and PBS-PAG groups, respectively), while IBO groups received IBO injections into the PFC or PAG (IBO-PFC and IBO-PAG groups, respectively). VARD was defined as a positive correlation (γ &gt; 0.4) between urine output rate and voided volume (VV).</p> Results <p>In both the PFC and PAG, numbers of c-Fos-positive cells were significantly higher in the High-rate group than in the Low-rate group (<i>p</i> &lt; 0.01 each). The IBO-PFC group exhibited decreased VV (<i>p</i> = 0.04) compared to the PBS-PFC group, although VARD was maintained (γ = 0.62). In contrast, the IBO-PAG group showed decreased VV (<i>p</i> = 0.04) compared to the PBS-PAG group and absence of VARD (γ = 0.17).</p> Conclusion <p>The PAG is responsible for VARD. Dysfunction of the PAG may contribute to OAB due to the absence of VARD.</p>

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Role of periaqueductal gray matter in bladder overactivity induced by vesical adaptation response to diuresis in rats

  • 期刊论文

  • 发表日期：

    2026年8月5日

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  • Yuki Harigane,
  • Hidenori Akaihata,
  • Akari Hiraguri,
  • Kei Yaginuma,
  • Akihisa Hasegawa,
  • Syunta Makabe,
  • Yu Endo,
  • Satoru Meguro,
  • Kanako Matsuoka,
  • Junya Hata,
  • Yuichi Sato,
  • Soichiro Ogawa,
  • Motohide Uemura,
  • Shigeki Kato,
  • Ryoji Fukabori,
  • Kazuto Kobayashi,
  • Yoshiyuki Kojima

摘要

Purpose

This study aimed to elucidate the pathophysiology of overactive bladder (OAB) associated with vesical adaptation response to diuresis (VARD), the homeostatic system adjusting bladder volume in response to diuresis, by identifying regulatory mechanisms for VARD in the brain.

Methods

Male 14-week-old Sprague–Dawley rats underwent cystometry with saline infused into the bladder at rates of 0 mL/h (Sham group), 1 mL/h (Low-rate group), or 10 mL/h (High-rate group). Neural activity in the prefrontal cortex (PFC) and periaqueductal gray (PAG) was assessed in each group using c-Fos staining. Effects of ibotenic acid (IBO) destruction of PFC or PAG lesions on VARD were compared using metabolic cage studies and cystometry, assuming that rates of bladder infusion and vesical filling were equal. Control groups received phosphate-buffered saline injections into the PFC or PAG (PBS-PFC and PBS-PAG groups, respectively), while IBO groups received IBO injections into the PFC or PAG (IBO-PFC and IBO-PAG groups, respectively). VARD was defined as a positive correlation (γ > 0.4) between urine output rate and voided volume (VV).

Results

In both the PFC and PAG, numbers of c-Fos-positive cells were significantly higher in the High-rate group than in the Low-rate group (p < 0.01 each). The IBO-PFC group exhibited decreased VV (p = 0.04) compared to the PBS-PFC group, although VARD was maintained (γ = 0.62). In contrast, the IBO-PAG group showed decreased VV (p = 0.04) compared to the PBS-PAG group and absence of VARD (γ = 0.17).

Conclusion

The PAG is responsible for VARD. Dysfunction of the PAG may contribute to OAB due to the absence of VARD.