Minocycline But Not Tigecycline Is Neuroprotective and Reduces the Neuroinflammatory Response Induced by the Superimposition of Sepsis Upon Traumatic Brain Injury*

Adembri, Chiara; Selmi, Valentina; Vitali, Luca; Tani, Akio; Margheri, Martina; Loriga, Beatrice; Carlucci, Martina; Nosi, Daniele; Formigli, Lucia; Gaudio, Angelo Raffaele De

doi:10.1097/ccm.0000000000000414

Cited by 44 publications

(28 citation statements)

References 49 publications

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“…In studies of CIPN, minocycline prevented CIPN-related symptoms and the activation of astrocytes despite the lack of microglial activation indicators [16][17][18][19] . Nevertheless, minocycline also possesses neuroprotective roles [20,28,45,46] . One notable characteristic of minocycline is that it has a direct effect on sodium channels in primary afferent neurons [47] , which suggests it has a role of peripheral analgesia.…”

Section: Bcp Induced By Walker 256 Mammary Carcinoma Cell Inocula Tionmentioning

confidence: 99%

“…Minocycline hydrochloride (purity>99%, S4226, Selleck Chemicals, Houston, TX, USA) was freshly dissolved in saline prior to each injection. The dose in the present experiment was selected based on previous relevant reports [27,28] and our preliminary results [29] . The drug solution was intrathecally injected in a volume of 10 μL, followed by a volume of 5 μL of saline to flush the catheter.…”

Section: Drug Administration Protocolmentioning

confidence: 99%

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Minocycline attenuates bone cancer pain in rats by inhibiting NF-κB in spinal astrocytes

et al. 2016

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Aim: To investigate the mechanisms underlying the anti-nociceptive effect of minocycline on bone cancer pain (BCP) in rats.Methods: A rat model of BCP was established by inoculating Walker 256 mammary carcinoma cells into tibial medullary canal. Two weeks later, the rats were injected with minocycline (50, 100 μg, intrathecally; or 40, 80 mg/kg, ip) twice daily for 3 consecutive days. Mechanical paw withdrawal threshold (PWT) was used to assess pain behavior. After the rats were euthanized, spinal cords were harvested for immunoblotting analyses. The effects of minocycline on NF-κB activation were also examined in primary rat astrocytes stimulated with IL-1β in vitro. Results: BCP rats had marked bone destruction, and showed mechanical tactile allodynia on d 7 and d 14 after the operation. Intrathecal injection of minocycline (100 μg) or intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced mechanical tactile allodynia. Furthermore, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of GFAP (astrocyte marker) and PSD95 in spinal cord. Moreover, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of NF-κB, p-IKKα and IκBα in spinal cord. In IL-1β-stimulated primary rat astrocytes, pretreatment with minocycline (75, 100 μmol/L) significantly inhibited the translocation of NF-κB to nucleus. Conclusion: Minocycline effectively alleviates BCP by inhibiting the NF-κB signaling pathway in spinal astrocytes.

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Section: Bcp Induced By Walker 256 Mammary Carcinoma Cell Inocula Tionmentioning

confidence: 99%

Section: Drug Administration Protocolmentioning

confidence: 99%

Minocycline attenuates bone cancer pain in rats by inhibiting NF-κB in spinal astrocytes

et al. 2016

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“…Maackia amurensis agglutinin (MAA) and Sambucus nigra agglutinin (SNA) digoxigenin (DIG) labeled lectins (Roche Diagnostic, Mannheim, Germany) were used to identify sialic acids linked α2–3 and α2–6 to galactose or galactosamine, respectively. Lectin histo-chemistry was performed as previously described [16, 17]. In short, sections were treated with 20% acetic acid to inhibit the endogenous alkaline phosphatase, then treated with 10% blocking reagent in Total Buffered Saline (TBS) to reduce the background labelling.…”

Section: Methodsmentioning

confidence: 99%

“…Sections were then rinsed in TBS, incubated with anti-digoxigenin, conjugated with alkaline phosphatase diluted in TBS and washed in TBS. Labelling of the sites containing bound lectin-digoxigenin was obtained by incubating slides with Buffer 2 containing nitroblue tetrazolium (NBT)/X-phosphate (Roche Diagnostics, Mannheim, Germany) [16, 18]. …”

Section: Methodsmentioning

confidence: 99%

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Changes in ceftriaxone pharmacokinetics/pharmacodynamics during the early phase of sepsis: a prospective, experimental study in the rat

Selmi¹,

Loriga²,

Vitali³

et al. 2016

J Transl Med

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BackgroundSepsis is characterized by the loss of the perm-selectivity properties of the glomerular filtration barrier (GFB) with consequent albuminuria. We examined whether the pharmacokinetics–pharmacodynamics (PK/PD) of ceftriaxone (CTX), an extensively protein-bound 3rd generation cephalosporin, is altered during early sepsis and whether an increase in urinary loss of bound-CTX, due to GFB alteration, can occur in this condition.MethodsA prospective, experimental, randomized study was carried out in adult male Sprague–Dawley rats. Sepsis was induced by cecal ligation and puncture (CLP). Rats were divided into two groups: Sham-operated and CLP. CTX (100 mg i.p., equivalent to 1 g dose in humans) was administered in order to measure plasma and lung CTX concentrations at several time-points: baseline and 1, 2, 4 and 6 h after administration. CTX was measured by High Performance Liquid Chromatography (HPLC). The morphological status of the sialic components of the GFB barrier was assessed by lectin histo-chemistry. Monte Carlo simulation was performed to calculate the probability of target attainment (PTA >90%) for 80 and 100% of Tfree > minimum inhibitory concentration (MIC) for 80 and 100% of dosing interval.Measurements and main resultsAfter CLP, sepsis developed in rats as documented by the growth of polymicrobial flora in the peritoneal fluid (≤1 × 101 CFU in sham rats vs 5 × 104–1 × 105 CFU in CLP rats). CTX plasma concentrations were higher in CLP than in sham rats at 2 and 4 h after administration (difference at 2 h was 47.3, p = 0.012; difference at 4 h was 24.94, p = 0.004), while lung penetration tended to be lower. An increased urinary elimination of protein-bound CTX occurred (553 ± 689 vs 149 ± 128 mg/L, p < 0.05; % of bound/total CTX 22 ± 6 in septic rats vs 11 ± 4 in sham rats, p < 0.01) and it was associated with loss of the GFB sialic components. According to Monte Carlo simulation a PTA > 90% for 100% of the dosing interval was reached neither for sham nor CLP rats using MIC = 1 mg/L, the clinical breakpoint for Enterobacteriacee.ConclusionsSepsis causes changes in the PK of CTX and an alteration in the sialic components of the GFB, with consequent loss of protein-bound CTX. Among factors that can affect drug pharmacokinetics during the early phases of sepsis, urinary loss of both free and albumin–bound antimicrobials should be considered.

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Development and validation of a liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) method for the quantification of tigecycline in rat brain tissues

Munyeza

Shobo

Baijnath

et al. 2015

Biomedical Chromatography

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Tigecycline (TIG), a derivative of minocycline, is the first in the novel class of glycylcyclines and is currently indicated for the treatment of complicated skin structure and intra-abdominal infections. A selective, accurate and reversed-phase high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for the determination of TIG in rat brain tissues. Sample preparation was based on protein precipitation and solid phase extraction using Supel-Select HLB (30 mg/1 mL) cartridges. The samples were separated on a YMC Triart C18 column (150 mm x 3.0 mm. 3.0 µm) using gradient elution. Positive electrospray ionization (ESI+) was used for the detection mechanism with the multiple reaction monitoring (MRM) mode. The method was validated over the concentration range of 150-1200 ng/mL for rat brain tissue. The precision and accuracy for all brain analyses were within the acceptable limit. The mean extraction recovery in rat brain was 83.6%. This validated method was successfully applied to a pharmacokinetic study in female Sprague Dawley rats, which were given a dose of 25 mg/kg TIG intraperitoneally at various time-points. Copyright © 2015 John Wiley & Sons, Ltd.

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Minocycline But Not Tigecycline Is Neuroprotective and Reduces the Neuroinflammatory Response Induced by the Superimposition of Sepsis Upon Traumatic Brain Injury*

Cited by 44 publications

References 49 publications

Minocycline attenuates bone cancer pain in rats by inhibiting NF-κB in spinal astrocytes

Minocycline attenuates bone cancer pain in rats by inhibiting NF-κB in spinal astrocytes

Changes in ceftriaxone pharmacokinetics/pharmacodynamics during the early phase of sepsis: a prospective, experimental study in the rat

Development and validation of a liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) method for the quantification of tigecycline in rat brain tissues

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