A Single Dose of Valproic Acid Improves Neurologic Recovery and Decreases Brain Lesion Size in Swine Subjected to an Isolated Traumatic Brain Injury

Traumatic brain injury (TBI)is a major cause of death and disability worldwide. Hemorrhagic shock (HS) aggravates tissue injury and complicates TBI recovery. We studied the combined insult of mild TBI and HS and investigated the impact of varying loss of blood volume on neurologic deficit and brain lesion volume. A novel positron emission tomography (PET) technique was employed to monitor tissue injury. Male Sprague Dawley rats received mTBI by controlled cortical impact (CCI) followed by withdrawal of 0%, 30-40%, 45%, or 50% of blood (mTBI, mTBI+HS≤40%, mTBI+HS45%, and mTBI+HS50%, respectively). Neurological deficit (mNSS= 5.6, 7.6, and 12.3) and mortality (2/12, 2/6, and 7/12) were higher in mTBI+HS≤40%, mTBI+HS45%, and mTBI+HS50%, than in mTBI alone rats (no death; mNSS=3.3). Histologic lesion size increased 3.5-fold in mTBI+HS50% compared to mTBI alone and the infarct-avid PET agent 18F-fluorodeoxyglucaric acid (FGA) proportionately detected tissue necrosis in mTBI+HS50% rats. Based on these results, we conclude that HS aggravates mTBI-induced neurological deficits, tissue injury and mortality. PET using 18F-FGA as an imaging marker can detect the extent of injury in a non-invasive manner.

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MRI Measurement of Angiogenesis and the Therapeutic Effect of Acute Marrow Stromal Cell Administration on Traumatic Brain Injury

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2012.106 ◽

2012 ◽

Vol 32 (11) ◽

pp. 2023-2032 ◽

Cited By ~ 16

Author(s):

Lian Li ◽

Michael Chopp ◽

Guang Liang Ding ◽

Chang Sheng Qu ◽

Qing Jiang Li ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Therapeutic Effect ◽

Brain Lesion ◽

Cerebral Atrophy ◽

Tissue Perfusion ◽

Acute Administration ◽

Transfer Constant ◽

Neurologic Recovery

Using magnetic resonance imaging (MRI), the present study was undertaken to investigate the therapeutic effect of acute administration of human bone marrow stromal cells (hMSCs) on traumatic brain injury (TBI) and to measure the temporal profile of angiogenesis after the injury with or without cell intervention. Male Wistar rats (300 to 350 g, n = 18) subjected to controlled cortical impact TBI were intravenously injected with 1 mL of saline ( n = 9) or hMSCs in suspension ( n = 9, 3 × 106 hMSCs) 6 hours after TBI. In-vivo MRI acquisitions of T2-weighted imaging, cerebral blood flow (CBF), three-dimensional (3D) gradient echo imaging, and blood-to-brain transfer constant (Ki) of contrast agent were performed on all animals 2 days after injury and weekly for 6 weeks. Sensorimotor function and spatial learning were evaluated. Volumetric changes in the trauma-induced brain lesion and the lateral ventricles were tracked and quantified using T2 maps, and hemodynamic alteration and blood–brain barrier permeability were monitored by CBF and Ki, respectively. Our data show that transplantation of hMSCs 6 hours after TBI leads to reduced cerebral atrophy, early and enhanced cerebral tissue perfusion and improved functional outcome compared with controls. The hMSC treatment increases angiogenesis in the injured brain, which may promote neurologic recovery after TBI.

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