Minocycline Attenuates Microglial Activation but Fails to Mitigate Degeneration in Inferior Olive and Pontine Nuclei After Focal Cerebellar Lesion M. T. Viscomi & L. Latini & F. Florenzano & G. Bernardi & M. Molinari Published online: 1 July 2008 # Springer Science + Business Media, LLC 2008 Abstract Degenerative changes in areas remote from the primary lesion site have been linked to the clinical outcome of focal brain damage, and inflammatory mechanisms have been considered to play a key role in the pathogenesis of these remote cell death phenomena. Minocycline is a tetracycline derivative, therapeutically effective in various experimental models of central nervous system (CNS) injuries that include inflammatory and apoptotic mechanisms, al- though recent findings have yielded mixed results. In this study, we investigated the effectiveness of minocycline treatment in reducing remote cell death. Glial activation and neuronal loss in precerebellar stations following cerebellar lesion were investigated using immunohistochemistry and Western blot techniques. Our results show that minocycline was effective in reducing microglial activations in axotomized precerebellar nuclei, but failed to mitigate either astrocytic response or neuronal loss. This finding supports the role of minocycline in modulating inflammatory response after CNS lesion and suggests its ineffectiveness in influencing degen- erative phenomena in areas remote from the primary lesion site. Keywords Remote cell death . Cerebellar lesion . Microglia . Inflammation . Astrocytes After focal brain damage, neuronal death is present in regions remote from the primary site of the lesion. These remote effects have been linked to antero- and retrograde degeneration in regions functionally related to the lesion site and have been considered an important outcome predictor [1]. Activated glial cells are suspected to play a key role in remote cell death by producing toxic mediators such as pro-inflammatory cytokines, nitric oxide, gluta- mate, and free radicals [2]. Microglial activation occurs very early in the injury process, and activated microglia exhibit morphological, molecular, and functional changes in response to a given injury. However, conditions dictating whether activated microglia exert a beneficial or a deleterious role are not completely understood [2, 3]. Given the above considerations, there is growing interest in treatments designed to modulate microglial response and inflammatory mechanisms in central nervous system (CNS) injury [4]. One of the compounds being investigated is the semisynthetic tetracycline derivate minocycline, widely adopted clinically as antimicrobial agent. Minocycline treatment confers neuroprotection after different types of CNS damage [5, 6]. In a model of global forebrain ischemia, minocycline has been suggested to act in a subregion-specific manner [7]. Very recently, minocycline treatment was effective in acute stroke in an open label clinical study [8]. However, reports have shown inconsis- tent and even detrimental effects of minocycline in different models of neurodegeneration [9, 10]. Consequently, the clinical importance of defining the contexts in which Cerebellum (2008) 7:401–405 DOI 10.1007/s12311-008-0042-z M. T. Viscomi : L. Latini : F. Florenzano : G. Bernardi : M. Molinari Santa Lucia Foundation I.R.C.C.S., Via del Fosso di Fiorano 65, 00143 Rome, Italy G. Bernardi Department of Neuroscience, University of Rome “Tor Vergata”, Viale Oxford 81, 00133 Rome, Italy M. Molinari (*) Experimental Neurorehabilitation Laboratory, Santa Lucia Foundation, Via Ardeatina 306, 00179 Rome, Italy e-mail: m.molinari@hsantalucia.it