Minocycline reduces reactive gliosis in the rat model of hydrocephalus

BMC Neuroscience

Zhanxiang Wang³  Feifei Zhang³  Caiquan Huang³  Feng Liu³  Hongwei Zhu³  Shaolin Zhang¹  Guowei Tan²  Hao Xu¹ 

[1]Medical College of Xiamen University, Xiamen, Fujian Province, 361003, China

[2]School of Life Science, Xiamen University, Xiamen, Fujian Province, 361003, China

[3]Department of Neurosurgery, First Affiliate Hospital of Xiamen University, Xiamen, Fujian Province, 361003, China

关键词: Minocycline;    Microgliosis;    Astrocytosis;    Gliosis;    Hydrocephalus;   

Others  :  1140697
DOI  :  10.1186/1471-2202-13-148

 received in 2012-05-29, accepted in 2012-11-23,  发布年份 2012

【 摘 要 】

Background

Reactive gliosis had been implicated in injury and recovery patterns associated with hydrocephalus. Our aim is to determine the efficacy of minocycline, an antibiotic known for its anti-inflammatory properties, to reduce reactive gliosis and inhibit the development of hydrocephalus.

Results

The ventricular dilatation were evaluated by MRI at 1-week post drugs treated, while GFAP and Iba-1were detected by RT-PCR, Immunohistochemistry and Western blot. The expression of GFAP and Iba-1 was significantly higher in hydrocephalic group compared with saline control group (p < 0.05). Minocycline treatment of hydrocephalic animals reduced the expression of GFAP and Iba-1 significantly (p < 0.05). Likewise, the severity of ventricular dilatation is lower in minocycline treated hydrocephalic animals compared with the no minocycline group (p < 0.05).

Conclusion

Minocycline treatment is effective in reducing the gliosis and delaying the development of hydrocephalus with prospective to be the auxiliary therapeutic method of hydrocephalus.

【 授权许可】

   
2012 Xu et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 1.

Figure 4.

Figure 5.

【 参考文献 】

• [1]Mangano FT, McAllister JP, Jones HC, Johnson MJ, Kriebel RM: The microglial response to progressive hydrocephalus in a model of inherited aqueductal stenosis. Neurol Res 1998, 20:697-704.
• [2]Khan OH, Enno TL, Del Bigio MR: Brain damage in neonatal rats following kaolin induction of hydrocephalus. ExpNeurol 2006, 200(2):311-320.
• [3]Miller JM, Kumar R, McAllister JP, Krause GS: Gene expression analysis of the development of congenital hydrocephalus in the H-Tx rat. Brain Res 2006, 1075:36-47.
• [4]Miller JM, McAllister JP: Reduction of astrogliosis and microgliosis by cerebrospinal fluid shunting in experimental hydrocephalus. Cerebrospinal Fluid Res 2007, 4:5. BioMed Central Full Text
• [5]Slobodian I, Krassioukov-Enns D, Del Bigio MR: Protein and synthetic polymer injection for induction of obstructive hydrocephalus in rats. Cerebrospinal Fluid Res 2007, 4:9. BioMed Central Full Text
• [6]Deren KE, Packer M, Forsyth J, Milash B, Abdullah OM, Hsu EW, McAllister JP: Reactive astrocytosis, microgliosis and inflammation in rats with neonatal hydrocephalus. ExpNeurol 2010, 226:110-119.
• [7]McAllister JP 2nd, Miller JM: Minocycline inhibits glial proliferation in the H-Tx rat model of congenital hydrocephalus. Cerebrospinal Fluid Res 2010, 27:7.
• [8]Yoshida Y, Koya G, Tamayama K, Kumanishi T, Abe S: Development of GFAP-positive cells and reactive changes associated with cystic lesions in HTX rat brain. Neurol Med Chir (Tokyo) 1990, 30(7):445-450.
• [9]Aoyama Y, Kinoshita Y, Yokota A, Hamada T: Neuronal damage in hydrocephalus and its restoration by shunt insertion in experimental hydrocephalus: a study involving the neurofilamentimmunostaining method. J Neurosurg 2006, 104:332-339.
• [10]Lopes LS, Slobodian I, DelBigio MR: Characterization of juvenile and young adult mice following induction of hydrocephalus with kaolin. ExpNeurol 2009, 219(1):187-196.
• [11]Tikka T, Fiebich BL, Goldsteins G, Keinanen R, Koistinaho J: Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia. J Neurosci 2001, 21:2580-2588.
• [12]Tikka TM, Koistinaho JE: Minocycline provides neuroprotection against n-methyl-d-aspartate neurotoxicity by inhibiting microglia. J Immunol 2001, 166:7527-7533.
• [13]Matsukawa N, Yasuhara T, Hara K, Xu L, Maki M, Yu G, Kaneko Y, Ojika K, Hess DC, Borlongan CV: Therapeutic targets and limits of minocycline neuroprotection in experimental ischemic stroke. BMC Neurosci 2009, 6:126.
• [14]Garwood CJ, Cooper JD, Hanger DP, Noble W: Anti-inflammatory impact of minocycline in a mouse model of tauopathy. Front Psychiatry 2010, 12:136.
• [15]Cai ZY, Yan Y, Chen R: Minocycline reduces astrocytic reactivation and neuroinflammation in the hippocampus of a vascular cognitive impairment rat model. Neurosci Bull 2010, 26:28-36.
• [16]Klein NC, Cunha BA: Tetracyclines. Med Clin N Am 1995, 79:789-801.
• [17]Power C, Henry S, Del Bigio MR, Larsen PH, Corbett D, Imai Y, Yong VW, Peeling J: Intracerebral hemorrhage induces macrophage activation and matrix metalloproteinases. Ann Neurol 2003, 53:731-742.
• [18]Nagra G, Li J, McAllister JP 2nd, Miller J: Impaired lymphatic cerebrospinal fluid absorption in a rat model of kaolin-induced communicating hydrocephalus. Am J PhysiolRegulIntegr Comp Physiol 2008, 294(5):R1752-R1759.
• [19]Wu J, Yang S, Xi G, Fu G, Keep RF, Hua Y: Minocycline reduces intracerebral hemorrhage-induced brain injury. Neurol Res 2009, 31(2):183-188.
• [20]Fagan SC, Edwards DJ, Borlongan CV, Xu L, Arora A, Feuerstein G, Hess DC: Optimal delivery of minocycline to the brain: implication for human studies of acute neuroprotection. ExpNeurol 2004, 186:248-251.
• [21]Evans WA: An encephalographic ratio for estimating ventricular enlargement and cerebral atrophy. Arch Neurol Psychiatry 1942, 47:931-937.
• [22]Liao CW, Fan CK, Kao TC, Ji DD, Su KE, Lin YH, Cho WL: Brain injury-associated biomarkers of TGF-beta1, S100B, GFAP, NF-L, tTG, AbetaPP, and tau were concomitantly enhanced and the UPS was impaired during acute brain injury caused by Toxocaracanis in mice. BMC Infect Dis 2008, 8:84. BioMed Central Full Text
• [23]Xu H, Zhang SL, Tan GW, Zhu HW, Huang CQ, Zhang FF, Wang ZX: Reactive GliosisandNeuroinflammation in Rats with Communicating Hydrocephalus. Neuroscience 2012, 218:317-325.
• [24]Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin-Phenol reagents. J BiolChem 1951, 193(1):265-275.
• [25]Li J, McAllister JP 2nd, Shen Y, Wagshul ME, Miller JM, Egnor MR, Johnston MG, Haacke EM, Walker ML: Communicating hydrocephalus in adult rats with obstruction of the basal cisterns or the cortical subarachnoid space. ExpNeurol 2008, 211(2):351-361.
• [26]Rekate HL: A consensus on the classification of hydrocephalus: its utility in the assessment of abnormalities of cerebrospinal fluid dynamics. Childs NervSyst 2011, 27(10):1535-1541.
• [27]Sofroniew MV: Molecular dissection of reactive astrogliosis and glial scar formation. Trends Neurosci 2009, 32:638-647.
• [28]Del Bigio MR, da Silva MC, Drake JM, Tuor UI: Acute and chronic cerebral white matter damage in neonatal hydrocephalus. Can J NeurolSci 1994, 21:299-305.
• [29]Albrechtsen M, Sorensen PS, Gjerris F, Bock E: High cerebrospinal fluid concentration of glial fibrillary acidic protein (GFAP) in patients with normal pressure hydrocephalus. J Neurol Sci 1985, 70:269-274.
• [30]Tullberg M, Blennow K, Mansson JE, Fredman P, Tisell M, Wikkelso C: Ventricular cerebrospinal fluid neurofilament protein levels decrease in parallel with white matter pathology after shunt surgery in normal pressure hydrocephalus. Eur J Neurol 2007, 14:248-254.
• [31]Petzold A, Keir G, Kerr M, Kay A, Kitchen N, Smith M, Thompson EJ: Early identification of secondary brain damage in subarachnoid hemorrhage: a role for glial fibrillary acidic protein. J Neurotrauma 2006, 23:1179-1184.
• [32]Beems T, Simons KS, Van Geel WJ, De Reus HP, Vos PE, Verbeek MM: Serum- and CSF-concentrations of brain specific proteins in hydrocephalus. ActaNeurochir 2003, 145:37-43.
• [33]Petzold A, Keir G, Green AJE, Giovannoni G, Thompson EJ: An ELISA for glial fibrillary acidic protein. J Immunol Meth 2004, 287:169-177.
• [34]Schipke CG, Boucsein C, Ohlemeyer C, Kirchhoff F, Kettenmann H: Astrocyte Ca2+ waves trigger responses in microglial cells in brain slices. FASEB J 2002, 16(2):255-257.
• [35]Ciccarelli R, Di Iorio P, D’Alimonte I, Giuliani P, Florio T, Caciagli F, Middlemiss PJ, Rathbone MP: Cultured astrocyte proliferation induced by extracellular guanosine involves endogenous adenosine and is raised by theco-presence of microglia. Glia 2000, 29:202-211.
• [36]John GR, Lee SC, Brosnan CF: Cytokines: Powerful regulators of glial cell activation. Neuroscientist 2003, 9:10-22.
• [37]Verderio C, Matteoli M: ATP mediates calcium signaling between astrocytes and microglial cells: modulation by IFN-γ. J Immunol 2001, 166:6383-6391.
• [38]Heales SJ, Lam AA, Duncan AJ, Land JM: Neurodegeneration or neuroprotection:the pivotal role of astrocytes. Neurochem Res 2004, 29:513-519.
• [39]Liu B, Hong JS: Role of microglia in inflammation-mediated neurodegenerative diseases: mechanisms and strategies for therapeutic intervention. J PharmacolExpTher 2003, 304:1-7.
• [40]Bruce-Keller AJ: Microglial–neuronal interactions in synaptic damage and recovery. J Neurosci Res 1999, 58:191-201.
• [41]Rennaker RL, Miller J, Tang H, Wilson DA: Minocycline increases quality and longevity of chronic neural recordings. J Neural Eng 2007, 4(2):L1-L5.
• [42]Ryu JK, Franciosi S, Sattayaprasert P, Kim SU, McLarnon JG: Minocycline inhibits neuronal death and glial activation induced by beta-amyloid peptide in rat hippocampus. Glia 2004, 48(1):85-90.
• [43]Filipovic R, Zecevic N: Neuroprotective role of minocycline in co-cultures of human fetal neurons and microglia. ExpNeurol 2008, 211:41-51.
• [44]Yenari MA, Xu L, Tang XN, Qiao Y, Giffard RG: Microglia potentiate damage to blood–brain barrier constituents: improvement by minocycline in vivo and in vitro. Stroke 2006, 37(4):1087-1093.
• [45]Padi SS, Kulkarni SK: Minocycline prevents the development of neuropathic pain, but not acute pain: possible anti-inflammatory and antioxidant mechanisms. Eur J Pharmacol 2008, 601(1–3):79-87.
• [46]Wasserman JK, Schlichter LC: Neuron death and inflammation in a rat model of intracerebral hemorrhage: Effects of delayed minocycline treatment. Brain Res 2007, 1136:208-218.
• [47]Siopi E, Cho AH, Homsi S, Croci N, Plotkine M, Marchand-Leroux C, Jafarian-Tehrani M: Minocycline restores sAPPα levels and reduces the late histopathological consequences of traumatic brain injury in mice. J Neurotrauma 2011, 28(10):2135-2143.