Minocycline reduces astrocytic reactivation and neuroinflammation in the hippocampus of a vascular cognitive impairment rat model

Cai, Zhiyou; Yan, Yongmin; Chen, Ran

doi:10.1007/s12264-010-0818-2

Cited by 70 publications

(44 citation statements)

References 42 publications

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“…Several lines of evidence have shown that minocycline, which has anti-inflammatory and neuroprotective properties, can accelerate the recovery of cognitive functions by inhibiting astrogliosis following cerebral ischemia, mu p75-saporin immunotoxic lesioning, and onset of Alzheimer's disease [5,14,16]. Minocycline also improves cognition and memory after cognitive impairment associated with traumatic brain injury [17], early-phase schizophrenia [18], chronic cerebral hypoperfusion [19], Alzheimer's disease [6], and phencyclidine-induced cognitive deficits [20].…”

Section: Discussionmentioning

confidence: 99%

“…Minocycline downregulated surgery-associated hippocampal tumor necrosis factor a, interleukin 1b, and interleukin 6 mRNA expression levels A previous study indicated that hippocampal expression levels of TNF-a and IL-1b were involved in the neuroprotective mechanism of minocycline against chronic cerebral ischemia [14]. We detected the hippocampal mRNA levels of TNF-a, IL-1b, and IL-6 using real-time PCR at the end of the experiment.…”

Section: Minocycline Inhibited Astrocytic Activation Induced By 70% Hmentioning

confidence: 93%

“…To examine partial hepatectomy-associated astrogliosis [13] and the role of minocycline in the inhibition of astrocyte activation in the hippocampus [14], we investigated changes in GFAP (a marker of astrocyte activation) and Iba1 (a marker of microglia activation) in the operation-treated hippocampus of mice using western blotting. Surgical interventions increased the expression level of GFAP in the hippocampus, but minocycline administration significantly inhibited this increase (Fig.…”

Section: Minocycline Inhibited Astrocytic Activation Induced By 70% Hmentioning

confidence: 99%

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Minocycline improves postoperative cognitive impairment in aged mice by inhibiting astrocytic activation

ShanWu¹,

Lu²,

Wenjie³

et al. 2013

NeuroReport

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Astrocytes are proving to be critical for the development of cognitive functions. In addition, astrocytic activation contributes toward cognitive impairment induced by chronic cerebral hypoperfusion. Minocycline has been shown to exhibit long-term neuroprotective effects in vascular cognitive impairment rat models through the inhibition of astrogliosis, and has shown potential for the prevention and treatment of postoperative cognitive decline in elderly patients. This study aimed to examine the effect of minocycline on hippocampal astrocytes and long-term postoperative cognitive dysfunction in aged mice. Mice were injected intraperitoneally with 45 mg/kg minocycline once a day for 30 days after 70% hepatectomy. Hippocampal-dependent spatial memory ability was evaluated using the Morris water maze. The expression levels of hippocampal glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule-1 were detected with western blotting, and the hippocampal mRNA relative expression levels of tumor necrosis factor a, interleukin 1 b (IL-1b), and IL-6 were tested using a real-time PCR. The Morris water maze test showed that escape latency and swim distance were prolonged significantly by the surgery, but the extent of impairment was mitigated by minocycline treatment. Hippocampal GFAP and mRNA of tumor necrosis factor a, IL-1b, and IL-6 showed corresponding changes that were consistent with the variations of spatial memory. Minocycline could alleviate hepatectomy-related long-term spatial memory impairment in aged mice, and was associated with reduced levels of hippocampal GFAP and proinflammatory cytokines resulting from astrocytic activation. NeuroReport

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Section: Discussionmentioning

confidence: 99%

Section: Minocycline Inhibited Astrocytic Activation Induced By 70% Hmentioning

confidence: 93%

Section: Minocycline Inhibited Astrocytic Activation Induced By 70% Hmentioning

confidence: 99%

See 1 more Smart Citation

Minocycline improves postoperative cognitive impairment in aged mice by inhibiting astrocytic activation

ShanWu¹,

Lu²,

Wenjie³

et al. 2013

NeuroReport

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“…In addition, studies using experimental models of stroke also reported protective effects of minocycline on astrogliosis (Leonardo et al 2008;Cai et al 2010). Simultaneously other investigators indicated its ineffectiveness on astrogliosis and astrocytic apoptosis in stroke model indicating a complex action of this drug under same inflammatory conditions (Yrjanheikki et al 1998;Matsukawa et al 2009).…”

Section: Introductionmentioning

confidence: 92%

Lipopolysaccharide-Induced Apoptosis of Astrocytes: Therapeutic Intervention by Minocycline

Sharma

Patro

2015

Cell Mol Neurobiol

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Astrocytes are most abundant glial cell type in the brain and play a main defensive role in central nervous system against glutamate-induced toxicity by virtue of numerous transporters residing in their membranes and an astrocyte-specific enzyme glutamine synthetase (GS). In view of that, a dysregulation in the astrocytic activity following an insult may result in glutamate-mediated toxicity accompanied with astrocyte and microglial activation. The present study suggests that the lipopolysaccharide (LPS)-induced inflammation results in significant astrocytic apoptosis compared to other cell types in hippocampus and minocycline could not efficiently restrict the glutamate-mediated toxicity and apoptosis of astrocytes. Upon LPS exposure 76 % astrocytes undergo degeneration followed by 44 % oligodendrocytes, 26 % neurons and 10 % microglia. The pronounced astrocytic apoptosis resulted from the LPS-induced glutamate excitotoxicity leading to their hyperactivation as evident from their hypertrophied morphology, glutamate transporter 1 upregulation and downregulation of GS. Therapeutic minocycline treatment to LPS-infused rats efficiently restricted the inflammatory response and degeneration of other cell types but could not significantly combat with the apoptosis of astrocytes. Our study demonstrates a novel finding on cellular degeneration in the hippocampus revealing more of astrocytic death and suggests a more careful consideration on the protective efficacy of minocycline.

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“…Further measures include maintaining a "normal" day-night rhythm, and maintaining the homeostasis by avoiding too long fasting before and after the procedure [7,11].Frequent visits by family and friends while the patient is still in the hospital and early discharge of patients to their own home environment also lead to a reduced incidence of POCD [7]. There are currently several studies investigating the influence of substances like dexamethason and minocycline [6].…”

Section: Postoperativelymentioning

confidence: 99%

Postoperative cognitive dysfunction in geriatric patients

2012

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Postoperative cognitive dysfunction (POCD) is a severe long-term complication after surgical procedures. POCD is mainly seen among geriatric patients. Hospitalization, extent of surgery, and systemic inflammatory response might contribute to POCD. The possible influence of the type of anesthesia is discussed. POCD is often not recognized; thus, incidence rates are likely to be underestimated (19-40%). POCD is associated with major consequences for the individual patient, e.g., delayed long-term recovery, reduced quality of life, and an increased mortality rate. Multiple risk factors have been identified over the last decade. However, the exact etiology is still unknown. This mini-review summarizes the recent developments concerning POCD prevention, diagnosis, and treatment.

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Minocycline reduces astrocytic reactivation and neuroinflammation in the hippocampus of a vascular cognitive impairment rat model

Cited by 70 publications

References 42 publications

Minocycline improves postoperative cognitive impairment in aged mice by inhibiting astrocytic activation

Minocycline improves postoperative cognitive impairment in aged mice by inhibiting astrocytic activation

Lipopolysaccharide-Induced Apoptosis of Astrocytes: Therapeutic Intervention by Minocycline

Postoperative cognitive dysfunction in geriatric patients

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