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Normal Pressure Hydrocephalus in Adult Mice Causes Gait Impairment, Cognitive Deficits, and Urinary Frequency with Incontinence
被引:0
作者:
Tish, Margaret M.
[1
,2
]
Voss, Natalie A.
[1
]
Bertolli, Aimee X.
[1
]
Klimara, Miles J.
[3
]
Smith, Richard J.
[3
]
Thedens, Daniel R.
[4
]
Allamargot, Chantal
[5
]
Hefti, Marco M.
[2
,6
]
Howard, Matthew A.
[7
]
Aldridge, Georgina M.
[1
,2
]
Geerling, Joel C.
[1
,2
]
机构:
[1] Univ Iowa, Dept Neurol, Iowa City, IA 52246 USA
[2] Iowa Neurosci Inst, Iowa City, IA 52246 USA
[3] Univ Iowa, Dept Otolaryngol, Iowa City, IA 52246 USA
[4] Univ Iowa, Dept Radiol, Iowa City, IA 52246 USA
[5] Univ Iowa, Cent Microscopy Res Facil, Iowa City, IA 52242 USA
[6] Univ Iowa, Dept Pathol, Iowa City, IA 52246 USA
[7] Univ Iowa, Dept Neurosurg, Iowa City, IA 52246 USA
来源:
关键词:
Hakim's triad;
gait apraxia;
kaolin;
magnetic gait;
micturition;
urinary urgency incontinence;
KAOLIN-INDUCED HYDROCEPHALUS;
EXPERIMENTAL OBSTRUCTIVE HYDROCEPHALUS;
CEREBROSPINAL-FLUID PRESSURE;
COMMUNICATING HYDROCEPHALUS;
CONGENITAL HYDROCEPHALUS;
INFLAMMATION MODEL;
SHUNT PLACEMENT;
WATER-CONTENT;
BRAIN;
RATS;
D O I:
10.1523/ENEURO.0412-24.2024.2
中图分类号:
Q189 [神经科学];
学科分类号:
071006 ;
摘要:
Normal pressure hydrocephalus (NPH) is marked by enlarged cerebral ventricles with normal intracranial pressure, plus three stereotypical symptoms: gait impairment, cognitive dysfunction, and urinary frequency with urge incontinence. The neural circuit dysfunction responsible for each of these symptoms remains unknown, and an adult mouse model would expand opportunities to explore these mechanisms in preclinical experiments. Here, we describe the first mouse model of chronic, communicating hydrocephalus with normal intracranial pressure. Hydrocephalic male and female mice had unsteady gait and reduced maximum velocity. Despite performing well on a variety of behavioral tests, they exhibited subtle learning impairments. Hydrocephalic mice also developed urinary frequency, and many became incontinent. This mouse model, with symptoms resembling human NPH, can be combined with molecular-genetic tools in any mouse strain to explore the neural circuit mechanisms of these symptoms. Preclinical work using this hydrocephalus model will lead to the development of new treatments for NPH symptoms.
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