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               Chinese herbal formulas attenuate cerebral edema and cognitive impairment

               in an experimental model of high-altitude cerebral edema


               Shu-Chun Liu,   1,2,3  De-Wei Lai *,4

               1  Department of Chinese Medicine, Chang Bing Show Chwan Memorial Hospital, Changhua,
                 Taiwan
               2  Doctoral Program in Translational Medicine, National Chung Hsing University, Taichung,
                 Taiwan
               3  Rong  Hsing  Translational  Medicine  Research  Center,  National  Chung  Hsing  University,
                 Taichung, Taiwan
               4  Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
               *  E-mail: deweilai123@gmail.com

               Abstract
                  A murine model of high-altitude cerebral edema (HACE) was successfully established by
               acute  hypobaric  hypoxia  (AHH)  through  mimic  rapid  ascent  to  5,000  m.  Compared  with
               controls,  AHH-exposed  mice  exhibited  pronounced  cerebral  edema,  elevated  brain  water
               content,  and  markedly  increased  blood–brain  barrier  (BBB)  permeability,  as  evidenced  by
               methylene  blue  extravasation  and  histological  analysis.  Treatment  with  Ling-Gui-Zhu-Gan
               Decoction  (LGZG),  Rhodiola  rosea,  or  Acetazolamide  (Diamox)  significantly  attenuated
               cerebral edema and reduced BBB leakage. Macroscopic brain observations and quantitative
               measurements  demonstrated  that  herbal-treated  groups  displayed  significantly  lower  brain
               water  content  and  vascular  permeability  relative  to  untreated  AHH  mice  (P  <  0.05).
               Hematoxylin–eosin  staining  further  confirmed  that  these  interventions  mitigated  neuronal
               injury and inflammatory cell infiltration. Among the tested prescriptions, LGZG exerted the
               most pronounced protective effects, supporting its potential utility in both prophylactic and
               therapeutic  contexts.  Furthermore,  Morris  Water  Maze  testing  and  histopathological
               assessments  revealed that  herbal  treatments  ameliorated cognitive deficits,  alleviated tissue
               injury, and improved the cerebral microenvironment under hypoxic stress. Collectively, these
               findings  demonstrate  that  LGZG  exerts  robust  neuroprotective  and  vasoprotective  effects
               against  AHH-induced  brain  injury,  offering  promising  strategies  for  the  prevention  and
               treatment of acute altitude sickness and HACE.

               Keywords:  High  altitude  cerebral  edema;  Acute  hypobaric  hypoxia;  Ling-Gui-Zhu-Gan
                           Decoction; Morris Water Maze
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