Minimal Long-Term Neurobehavioral Impairments after Endovascular Perforation Subarachnoid Hemorrhage in Mice

Fanizzi, Claudia; Sauerbeck, Andrew D.; Gangolli, Mihika; Zipfel, Gregory J.; Brody, David L.

doi:10.1038/s41598-017-07701-y

Cited by 12 publications

(3 citation statements)

References 47 publications

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“…Thirty percent of survivors exhibit outcomes with the least clinical benefit and are left with significant neurobehavioral impairments such as gait dysfunction 25,26 . Knowing this, it is of great importance to study the underlying pathological mechanisms of the disease and to devise novel therapeutic interventions using the experimentally tractable mammalian model of SAH 27 …”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of gait parameters and gene expression profiles in a murine model of subarachnoid hemorrhage

Zheng

Lü

Xiong

et al. 2021

Genes Brain and Behavior

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Gait analysis has been widely used to examine the behavioral presentation of numerous neurological disorders. Thorough murine model evaluation of the subarachnoid hemorrhage (SAH)‐associated gait deficits is missing. This study measures gait deficits using a clinically relevant murine model of SAH to examine associations between gait variability and SAH‐associated gene expressions. A total of 159 dynamic and static gait parameters from the endovascular perforation murine model for simulating clinical human SAH were determined using the CatWalk system. Eighty gait parameters and the mRNA expression levels of 35 of the 88 SAH‐associated genes were differentially regulated in the diseased models. Totals of 42 and 38 gait parameters correlated with the 35 SAH‐associated genes positively and negatively with Pearson's correlation coefficients of >0.7 and <−0.7, respectively. p‐SP1453 expression in the motor cortex in SAH animal models displays a significant correlation with a subset of gait parameters associated with muscular strength and coordination of limb movements. Our data highlights a strong correlation between gait variability and SAH‐associated gene expression. p‐SP1453 expression could act as a biomarker to monitor SAH pathological development and a therapeutic target for SAH.

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Section: Discussionmentioning

confidence: 99%

Integrated analysis of gait parameters and gene expression profiles in a murine model of subarachnoid hemorrhage

Zheng

Lü

Xiong

et al. 2021

Genes Brain and Behavior

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“…Thus, a total of 0.1 ml of iohexol (300 mg/ml) was injected into the cisterna magna of rats, as described in a previous study. 1 , 5 , 7) The contrast agent was replaced with 0.1 ml physiological saline in the control group.…”

Section: Study Protocolmentioning

confidence: 99%

“…These include direct injection of autologous blood into the cisterna magna, 5) transection of a vein in the cistern, 6) or arterial perforation in the circle of Willis using an endovascular filament inserted through the external carotid artery (ECA; endovascular perforation [EP] model). [7][8][9][10][11][12][13] Among them, the EP model has been commonly used in basic research on SAH because it mimics the rupture of a cerebral aneurysm and most of its sequelae, such as brain edema formation, 11,14) delayed cerebral vasospasm (CVS), 15,16) and neurological dysfunction. 17,18) However, due to the drawbacks of large variations in the amount of bleeding, the results of these experiments require the evaluation of the severity.…”

Section: Introductionmentioning

confidence: 99%

Intra-arterial Contrast-enhanced Micro-computed Tomography Can Evaluate Intracranial Status in the Ultra-early Phase of Experimental Subarachnoid Hemorrhage in Rats

Miyaoka

Yamamoto

Miyachi

et al. 2021

Neurol. Med. Chir.(Tokyo)

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The endovascular perforation (EP) model is a common technique for experimental subarachnoid hemorrhage (SAH) in rats, simulating the pathophysiological features observed in the acute phase of SAH. Due to the drawbacks of large variations in the amount of bleeding, the results obtained from this model require severity evaluation. However, no less-invasive procedure could confirm the precise intracranial conditions immediately after establishing the rat EP model. We created a novel method for evaluating SAH immediately after establishing the rat EP model using intra-arterial contrast-enhanced micro-computed tomography (CT). We administered contrast agents continuously via the carotid artery during surgery and performed CT examination immediately after SAH induction. First, bleeding severity was classified by establishing a scoring system based on the CT findings (cSAH scoring system). Subsequently, we determined the actual SAH distribution macroscopically and histologically and compared it with the cSAH scores. Second, we investigated the contrast agent's neurotoxicity in rats. Finally, we confirmed the correlation between cSAH scores and SAH severity, including neurological status, cerebral vasospasm, and hematoma volume 24 hr after SAH. Intra-arterial contrast-enhanced micro-CT could visualize the distribution of SAH proportionally to the bleeding severity immediately after establishing the EP model. Moreover, the contrast agent administration was determined not to be neurotoxic to rats. The cSAH scoring revealed a significant correlation with the SAH severity in the rat EP model (P <0.01). Thus, our minimally invasive method provided precise information on intracranial status in the ultra-early phase of SAH in rats EP model.

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Development and Validation of a Prechiasmatic Mouse Model of Subarachnoid Hemorrhage to Measure Long‐Term Cognitive Deficits

Diwan,

Mehla,

Nelson

et al. 2024

Advanced Science

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Controllable and reproducible animal models of aneurysmal subarachnoid hemorrhage (SAH) are crucial for the systematic study of the pathophysiology and treatment of this debilitating condition. However, current animal models have not been successful in replicating the pathology and disabilities seen in SAH patients, especially the long‐term neurocognitive deficits that affect the survivor's quality of life. Therefore, there is an unmet need to develop experimental models that reliably replicate the long‐term clinical ramifications of SAH – especially in mice where genetic manipulations are straightforward and readily available. To address this need, a standardized mouse SAH model is developed that reproducibly produced significant and trackable long‐term cognitive deficits. SAH is induced by performing double blood injections into the prechiasmatic cistern – a simple modification to the well‐characterized single prechiasmatic injection mouse model of SAH. Following SAH, mice recapitulated key characteristics of SAH patients, including cerebral edema measured by MRI ‐ an indicator of early brain injury (EBI), neuroinflammation, apoptosis, and long‐term cognitive impairment. This newly developed SAH mouse model is considered an ideal paradigm for investigating the complex SAH pathophysiology and identifying novel druggable therapeutic targets for treating SAH severity and SAH‐associated long‐term neurocognitive deficits in patients.

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Minimal Long-Term Neurobehavioral Impairments after Endovascular Perforation Subarachnoid Hemorrhage in Mice

Cited by 12 publications

References 47 publications

Integrated analysis of gait parameters and gene expression profiles in a murine model of subarachnoid hemorrhage

Integrated analysis of gait parameters and gene expression profiles in a murine model of subarachnoid hemorrhage

Intra-arterial Contrast-enhanced Micro-computed Tomography Can Evaluate Intracranial Status in the Ultra-early Phase of Experimental Subarachnoid Hemorrhage in Rats

Development and Validation of a Prechiasmatic Mouse Model of Subarachnoid Hemorrhage to Measure Long‐Term Cognitive Deficits

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