Shock/Sepsis/Trauma/Critical careThe role of neuropeptide Y and aquaporin 4 in the pathogenesis of intestinal dysfunction caused by traumatic brain injury
Introduction
Although the exact incidence is unknown, traumatic brain injury (TBI) can lead to intestinal dysfunction [1]. Its symptoms include anorexia, dyspepsia, abdominal distension, and constipation. Some studies suggest that TBI causes gastrointestinal ischemia and edema [2]. Neuropeptide Y (NPY) is a strong vasoconstrictor [3], and aquaporin 4 (AQP4) plays an important role in the regulation of the intracellular and interstitial water content [4]. Little is known about the interaction between NPY and AQP4 and their roles in intestinal dysfunction after TBI. This study was designed to test the hypothesis that TBI increases the excitability of the sympathetic nervous system, causing an increase in NPY production by sympathetic nerve endings. The subsequent increase in plasma NPY concentrations acts on the intestinal vessels, leading to vascular spasms and contraction, intestinal ischemia, intestinal epithelial cell and intestinal smooth muscle cell hypoxia, and intracellular aerobic metabolic disorders. Increased intracellular concentrations of acidic metabolites such as lactic acid then increase the intracellular osmotic pressure and stimulate AQP4 gene and protein expression, which then increases the membrane permeability for water molecules to reduce the concentrations of intracellular acidic metabolites, protect the organelles, and maintain normal organelle functions. However, the increased influx of water into the cells may lead to cell edema, organelle swelling, increased tension of cell and organelle membranes, and even rupture of the cell membrane and organelle disintegration. This then seriously affects intestinal functions such as the secretion of digestive juices, absorption of nutrients, and intestinal peristalsis.
Section snippets
Experimental animals and grouping
The study was performed according to the guidelines of the Institutional Animal Care Committee of Shanxi Medical University (Taiyuan, China). Forty adult healthy male Wistar rats weighing 280 ± 10 g were obtained from the Animal Center of Shanxi Medical University. The animals were randomly divided into a control group (C, n = 10), a mild trauma group (M1, n = 10), a moderate trauma group (M2, n = 10), and a severe trauma group (S, n = 10).
Animal model and sample preparation
TBI was induced as previously described [5]. Briefly,
Jejunum histology
The specimens of the control group showed normal and typical leaf-like villi crypts. In contrast, the specimens from the mild, moderate, and severe groups showed different degrees of structural changes, ranging from swelling and degeneration of villous epithelial cells to extensive denudation and collapse of the villi. The more severe the grade of trauma, the more serious the degree of intestinal mucosal injury. Similarly, intestinal smooth muscle also showed varying degrees of edema and
Discussion
Although the exact incidence is unknown, TBI can lead to intestinal dysfunction. At present the pathologic mechanism is not yet clear. Some studies speculated that TBI affects gastrointestinal function through the hypothalamus-pituitary-adrenal axis, brain-gut peptides, the vagus nerve in the medulla oblongata, and cytokine pathways [1]. Hang et al. found that some brain-gut peptides in the plasma and small intestine changed significantly after TBI [6]. For example, the concentration of
Acknowledgment
This study was supported by the National Natural Science Foundation Youth Fund (Fund No. 30600637), the Shanxi Province Basic Research Program Youth Science and Technology Research Fund (Fund No. 2010021034-4), the Shanxi Scholarship Council of China (No. 2011-096), and the Technology Innovation Fund of Shanxi Medical University (No. 01201010).
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