Effects of pituitary adenylate cyclase activating polypeptide on CD4+/CD8+ T cell levels after traumatic brain injury in a rat model

doi:10.5847/wjem.j.issn.1920-8642.2012.04.010

Abstract

Abstract:

BACKGROUND: The effect of pituitary adenylate cyclase activating polypeptide (PACAP) during traumatic brain injury (TBI) and whether it can modulate secondary injury has not been reported previously. The present study evaluated the potential protective effects of ventricular infusion of PACAP in a rat model of TBI.

METHODS: Male Sprague Dawley rats were randomly divided into 3 treatment groups (n=6, each): sham-operated, vehicle (normal saline)+TBI, and PACAP+TBI. Normal saline or PACAP (1 μg/5 μL) was administered intracerebroventricularly 20 minutes before TBI. Right parietal cortical contusion was produced via a weight-dropping method. Brains were extracted 24 hours after trauma. Histological changes in brains were examined by HE staining. The numbers of CD4⁺ and CD8⁺ T cells in blood and the spleen were detected via flow cytometry.

RESULTS: In injured brain regions, edema, hemorrhage, inflammatory cell infiltration, and swollen and degenerated neurons were observed under a light microscope, and the neurons were disorderly arrayed in the hippocampi. Compared to the sham group, average CD4⁺ CD8^- lymphocyte counts in blood and the spleen were significantly decreased in rats that received TBI+vehicle, and CD4^- CD8⁺ were increased. In rats administered PACAP prior to TBI, damage was attenuated as evidenced by significantly increased CD4⁺, and decreased CD8⁺, T lymphocytes in blood and the spleen.

CONCLUSION: Pretreatment with PACAP may protect against TBI by influencing periphery T cellular immune function.

Key words: Traumatic brain injury, Pituitary adenylate cyclase activating polypeptide, CD4⁺ T lymphocyte, CD8⁺ T lymphocyte, Rat, Spleen, Blood, Flow cytometry

Rong Hua, Shan-shan Mao, Yong-mei Zhang, Fu-xing Chen, Zhong-hai Zhou, Jun-quan Liu. Effects of pituitary adenylate cyclase activating polypeptide on CD4⁺/CD8⁺ T cell levels after traumatic brain injury in a rat model[J]. World Journal of Emergency Medicine, 2012, 3(4): 294-298.

Figures/Tables 6

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References 22

1	Yong VW, Rivest S. Taking advantage of the systemic immune system to cure brain diseases. Neuron 2009; 64:55-60. doi: 10.1016/j.neuron.2009.09.035
2	Bourgault S, Vaudry D, Dejda A, Doan ND, Vaudry H, Fournier A. Pituitary adenylate cyclase-activating polypeptide: focus on structure-activity relationships of a neuroprotective Peptide. Curr Med Chem 2009; 16:4462-4480. doi: 10.2174/092986709789712899 pmid: 19835562
3	Sanchez A, Chiriva-Internati M, Grammas P. Transduction of PACAP38 protects primary cortical neurons from neurotoxic injury. Neurosci Lett 2008; 448:52-55. doi: 10.1016/j.neulet.2008.10.021 pmid: 18938212
4	Kato H, Ito A, Kawanokuchi J, Jin S, Mizuno T, Ojika K. et al. Pituitary adenylate cyclase-activating polypeptide (PACAP) ameliorates experimental autoimmune encephalomyelitis by suppressing the functions of antigen presenting cells. Mult Scler 2004; 10:651-659. doi: 10.1191/1352458504ms1096oa pmid: 15584490
5	Paxinos G, Watson C. The rat brain in sterotaxic coordinates. 2nd ed. Sydney: Academic Press, 1986: F23-26.
6	Feeney DM, Boyeson MG, Linn RT, Murray HM, Dail WG. Responses to cortical injury: I. Methodology and local effects of contusions in the rat. Brain Res 1981; 211:67-77. doi: 10.1016/0006-8993(81)90067-6 pmid: 7225844
7	Werner C, Engelhard K. Pathophysiology of traumatic brain injury. Br J Anaesth 2007; 99:4-9. doi: 10.1093/bja/aem131 pmid: 17573392
8	Liu SL, Wang ZP, Zeng YM, Jiang S, Wang SQ. Relation between GLu-R and the protective effect of hypothermia on oxygen and glucose deprivation injury in hippocampal slice or rat. Zhongguo Ying Yong Sheng Li Xue Za Zhi 2005; 21:127-132. pmid: 21171321
9	Schibler A, Humphreys S. Increased brain tissue oxygen tension in children with traumatic brain injury using temperature-corrected guided ventilation during prophylactic hypothermia. Crit Care Resusc 2012; 14:20-24.
10	Miyata A, Arimura A, Dahl RR, Minamino N, Uehara A, Jiang L. et al. Isolation of a novel 38 residue-hypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells. Biochem Biophys Res Commun 1989; 164:567-574. doi: 10.1016/0006-291x(89)91757-9 pmid: 2803320
11	Vaudry D, Falluel-Morel A, Bourgault S, Basille M, Burel D, Wurtz O. et al. Pituitary adenylate cyclase- activating polypeptide and its receptors: 20 years after the discovery. Pharmacol Rev 2009; 61:283-357. doi: 10.1124/pr.109.001370 pmid: 19805477
12	Sanchez A, Chiriva-Internati M, Grammas P. Transduction of PACAP38 protects primary cortical neurons from neurotoxic injury. Neurosci Lett 2008; 448:52-55. doi: 10.1016/j.neulet.2008.10.021 pmid: 18938212
13	Kovesdi E, Tamas A, Reglodi D, Farkas O, Pál J, Tóth G. et al. Posttraumatic administration of pituitary adenylate cyclase activating polypeptide in central fluid percussion injury in rats. Neurotox Res 2008; 13:71-78. doi: 10.1007/BF03033558
14	Kato H, Ito A, Kawanokuchi J, Jin S, Mizuno T, Ojika K. et al. Pituitary adenylate cyclase-activating polypeptide (PACAP) ameliorates experimental autoimmune encephalomyelitis by suppressing the functions of antigen presenting cells. Mult Scler 2004; 10:651-659. doi: 10.1191/1352458504ms1096oa pmid: 15584490
15	Lv B, Tang Y, Chen F, Xiao X. Vasoactive intestinal Peptide and pituary adenylate cyclase-activating polypeptide inhibit tissue factor expression in monocyte in vitro and in vivo. Shock 2009; 31:185-191. doi: 10.1097/SHK.0b013e31817d423a pmid: 18650785
16	Mrakovcic-Sutic I, Tokmadzic VS, Laskarin G, Mahmutefendic H, Lucin P, Zupan Z. et al. Early changes in frequency of peripheral blood lymphocyte subpopulations in severe traumatic brain-injured patients. Scand J Immunol 2010; 72:57-65. doi: 10.1111/j.1365-3083.2010.02407.x pmid: 20591077
17	Delgado M, Ganea D. VIP and PACAP inhibit Fas ligand-mediated bystander lysis by CD4(+) T cells. J Neuroimmunol 2001; 112:78-88. doi: 10.1016/s0165-5728(00)00414-8 pmid: 11108936
18	Hobbs TR, O'Malley JP, Khouangsathiene S, Dubay CJ. Comparison of lactate, base excess, bicarbonate, and pH as predictors of mortality after severe trauma in rhesus macaques (Macaca mulatta). Comp Med 2010; 60:233-229. pmid: 20579439
19	Siveen KS, Kuttan G. Effect of Aerva lanata on cell-mediated immune responses and cytotoxic T-lymphocyte generation in normal and tumor-bearing mice. J Immunotoxicol 2012; 9:25-33.Epub 2011 Nov 30. doi: 10.3109/1547691X.2011.609191
20	Ganea D, Rodriguez R, Delgado M. Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: players in innate and adaptive immunity. Cell Mol Biol (Noisy-le-grand) 2003; 49:127-142.
21	Ganea D, Delgado M. The neuropeptides VIP/PACAP and T cells: inhibitors oractivators? Curr Pharm Des 2003; 9:997-1004. doi: 10.2174/1381612033455116 pmid: 12678866
22	Delgado M, Ganea D. Anti-inflammatory neuropeptides: a new class of endogenous immunoregulatory agents. Brain Behav Immun 2008; 22:1146-1151. doi: 10.1016/j.bbi.2008.06.001

Group	CD4⁺ T cells	CD8⁺ T cells
Sham	59.57±4.97	13.54±4.51
NS+TBI	39.20±2.44^*	24.62±6.27^*
PACAP+TBI	48.26±6.29^#	18.34±5.09

Groups	CD4⁺ T cells	CD8⁺ T cells
Sham	43.14±3.73	17.43±3.76
NS+ TBI	25.74±4.46^#	23.26±4.13^#
PACAP+ TBI	28.37±11.93^*	19.49±2.11

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