Minocycline as a Neuroprotective Agent

Stirling, David P.; Koochesfahani, Kaveh M.; Steeves, John D.; Tetzlaff, Wolfram

doi:10.1177/1073858405275175

Cited by 248 publications

(157 citation statements)

References 107 publications

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“…To elucidate its neuroprotective effect, we also incorporated two other agents, i.e., methylprednisolone (MP), that is the only proven clinically used agent, and minocycline (MC), that is a derivative of tetracycline and has been shown to mediate neuroprotection in various experimental models of CNS diseases. Furthermore, MC has been shown to have antiapoptotic and anti-inflammatory effects [15,23,24,28].…”

Section: Introductionmentioning

confidence: 99%

Pregabalin as a neuroprotector after spinal cord injury in rats

Kim

Rhyu

et al. 2008

Eur Spine J

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The over-expression of excitotoxic neurotransmitter, such as glutamate, is an important mechanism of secondary injury after spinal cord injury. The authors examined the neuroprotective effect of pregabalin (GP) which is known as to reduce glutamate secretion, in a rat model of spinal cord injury. Thirty-two male SpragueDawley rats were randomly allocated to four groups; the control group (contusion injury only), the methylprednisolone treated group, the minocycline treated group and the GP treated group. Spinal cord injury was produced by contusion using the New York University impactor (25 gcm, at the 9th-10th thoracic). Functional evaluations were done using the inclined plane test and a motor rating scale. Anti-apoptotic and anti-inflammatory effects were evaluated by in situ nick-end labeling staining technique (TUNEL) and immunofluorescence staining of cord tissues obtained at 7 days post-injury. Pregabalin treated animals showed significantly better functional recovery, and antiapoptotic and anti-inflammatory effects. Mean numbers of TUNEL positive cells in the respective groups were 63.5 ± 7.4, 53.6 ± 4.0, 44.2 ± 3.9 and 36.5 ± 3.6. Double staining (TUNEL and anti-CC1) for oligodendrocyte apoptosis, was used to calculate oligodendrocyte apoptotic indexes (AI), using the following formula AI = (No. of doubly stained cells/No. of anti-CC1 positive cells) 9 100.Mean group AIs were 88.6, 46.7, 82.1 and 70.3%, respectively. Mean numbers of activated microglia (anti-OX-42 positive cells) in high power fields were 29.8 ± 3.9, 22.7 ± 4.1, 21.0 ± 3.9 and 17.8 ± 4.3, respectively. This experiment demonstrates that GP can act as a neuroprotector after SCI in rats, and its anti-apoptotic and anti-inflammatory effects are related to its neuroprotective effect. Further studies are needed to unveil the specific mechanism involved at the receptor level.

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Section: Introductionmentioning

confidence: 99%

Pregabalin as a neuroprotector after spinal cord injury in rats

Kim

Rhyu

et al. 2008

Eur Spine J

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“…inhibition of p38 MAPK activation in microglia or with prevention of apoptosis by the inhibition of caspase activation (Stirling et al 2005). Activated caspase-3 in the spinal cord milieu is reduced by minocycline during the first 24-72 hours after a mid-thoracic spinal cord injury and is associated with functional improvement and spinal cord tissue sparing up to 4 weeks after injury (Lee et al 2003;Festoff et al 2006).…”

Section: Discussionmentioning

confidence: 99%

“…However, in some studies, minocycline treatment has failed to demonstrate beneficial effects (Smith et al 2003;Fernandez-Gomez et al 2005). Although its mechanisms of action are not fully understood, some studies suggest that minocycline may prevent cell death by suppressing the apoptotic pathway (Stirling et al 2005). Minocycline may also influence non-apoptotic responses to nerve injury.…”

Section: Introductionmentioning

confidence: 99%

Minocycline protects motor but not autonomic neurons after cauda equina injury

Hoang

Akhavan

et al. 2008

Exp Brain Res

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Conus medullaris/cauda equina injuries typically result in loss of bladder, bowel, and sexual functions, partly as a consequence of autonomic and motor neuron death. To mimic these injuries, we previously developed a rodent lumbosacral ventral root avulsion (VRA) injury model, where both autonomic and motor neurons progressively die over several weeks. Here, we investigate whether minocycline, an antibiotic with putative neuroprotective effects, may rescue degenerating autonomic and motor neurons after VRA injury. Adult female rats underwent lumbosacral VRA injuries followed by a 2-week treatment with either minocycline or vehicle injected intraperitoneally. The sacral segment of the spinal cord was studied immunohistochemically using choline acetyltransferase (ChAT) and activated caspase-3 at 4 weeks post-operatively. Minocycline increased the survival of motoneurons but not preganglionic parasympathetic neurons (PPNs). Further investigations demonstrated that a larger proportion of motoneurons expressed activated caspase-3 compared to PPNs after VRA injury and indicated an association with minocycline's differential neuroprotective effect. Our findings suggest that minocycline may protect degenerating motoneurons and expand the therapeutic window of opportunity for surgical repair of proximal root lesions affecting spinal motoneurons.

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“…These modifications to the core structure increase its half-life in comparison to first generation tetracyclines and have improved the absorption of minocycline into the central nervous system and its penetration into cerebrospinal fluid. 6 Minocycline has a low propensity to produce antibiotic resistance and is commonly used in the treatment of acne, rosacea and other infections of the skin and respiratory tract. 7 In addition to its antibiotic properties, studies over the past 11 years have shown that minocycline has significant neuroprotective effects in pre-clinical studies of neurodegenerative disease.…”

Section: Introductionmentioning

confidence: 99%

“…Minocycline has now been shown to reduce disease progression, inhibit neuronal death and increase the life-span of rodents that recapitulate features of neurodegenerative and neurological disorders including PD, HD, MND, multiple sclerosis, spinal cord injury, AD and related tauopathies and central and peripheral prion infections. [9][10][11] has shown that minocycline is effective in reducing the development of abnormal tau species and tau aggregation in htau mice. 9 The htau transgenic animals express human wild-type tau and progressively develop hyperphosphorylated tau aggregates and NFTs in the hippocampus and cortex.…”

Section: Introductionmentioning

confidence: 99%

Minocycline as a potential therapeutic agent in neurodegenerative disorders characterized by protein misfolding

Noble

Garwood

Hanger

2009

Prion

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Many neurodegenerative disorders share common features including the accumulation of aggregated misfolded proteins, neuroinflammation and the induction of apoptosis. While the contributions of each of these individual elements to neuronal death remain unclear, a commonly used antibiotic, minocycline, has been shown to reduce the progression and severity of disease in several models of neurodegeneration by variously downregulating these molecular pathways. Here we discuss the evidence for the potential of minocycline as a broad-specificity therapeutic agent for those neurodegenerative diseases that are characterized by the presence of misfolded proteins.

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Minocycline as a Neuroprotective Agent

Cited by 248 publications

References 107 publications

Pregabalin as a neuroprotector after spinal cord injury in rats

Pregabalin as a neuroprotector after spinal cord injury in rats

Minocycline protects motor but not autonomic neurons after cauda equina injury

Minocycline as a potential therapeutic agent in neurodegenerative disorders characterized by protein misfolding

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