Intracranial Hemorrhage: Mechanisms of Secondary Brain Injury

Lok, Josephine; Leung, Wendy; Murphy, Sarah; Butler, William E.; Noviski, Natan; Lo, Eng H.

doi:10.1007/978-3-7091-0693-8_11

Cited by 105 publications

(87 citation statements)

References 67 publications

(83 reference statements)

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“…brain tissue mediated by glutamate activation of NMDA or AMPA receptors results in a widening of the secondary neuronal damage in the different brain regions (Lee et al 1999;Liu et al 2007;Lau and Tymianski 2010;Lai et al 2011;Lok et al 2011). The findings of the study showed how fast the waves of excitotoxicity spread in the brain tissue after contact with blood.…”

Section: Discussionmentioning

confidence: 83%

“…Evidently, leucocytes may cause a whole-brain injury immediately after ICH (Wagner et al 2005). They have important effects in early releasing of pro-inflammatory mediators and the platelet-leukocyte-endothelial cell interactions after hemorrhage (MacKenzie and Clayton 1999;Nishikawa et al 2009;Lok et al 2011). Apparently, the role of the leucocytes actually consisted in the NMDA receptors firing in combination with their secondary effects.…”

Section: Perfusion Of Slices With Fraction Of Leucocytesmentioning

confidence: 99%

“…The ionotropic receptors are linked to multiple intracellular messengers, such as Ca 2+ , cyclic AMP, reactive oxygen species, and initiate multiple signaling cascades that determine the neuronal survival during brain damage (Michaelis, 1998;Lai et al 2011;Lok et al 2011). Excessive NMDA receptors activation in neurons leads to the production of ROS and to endothelial excitotoxicity associated with a loss of the cerebral endothelial barrier dysfunction and edema formation Betzen et al 2009).…”

Section: How Ferric Ions Influence On Synaptic Activity In Piriform Cmentioning

confidence: 99%

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Effects of the blood components on the AMPA and NMDA synaptic responses in brain slices in the onset of hemorrhagic stroke

Mokrushin¹,

Pavlinova²

2013

gpb

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Abstract. Blood-borne events play a major role in post bleeding disturbances of the neuronal network. However, very little is known about the early effects of blood plasma, leucocytes, and the red blood cells on the AMPA and NMDA-mediated synaptic responses in the onset of experimental intracranial hemorrhage (ICH). In this study, we used the technique of on-line monitoring of electrophysiological parameters referred to synaptic activity in piriform cortex of SHR rat slice. We exposed the olfactory cortex slices to diluted autologous blood or its components and compared with effects of ferric chloride. Whole blood exerted a total inhibition of synaptic activity in piriform cortex within first 5 min. Dilution of blood induced prolonged epileptic synaptic activation of NMDA receptors. Blood plasma and fraction of leucocytes induced hyperactivation of neurons transforming to epileptiform discharges. Fraction of red blood cells acted biphasic, an initial sharp activity of AMPA-and NMDAmediated receptors replaced by a following total depression. Our slice-based models of experimental stroke revealed the mechanism of the earliest pathophysiologic events occur in brain tissue during bleeding that may be relevant to the human ICH.

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Section: Discussionmentioning

confidence: 83%

Section: Perfusion Of Slices With Fraction Of Leucocytesmentioning

confidence: 99%

Section: How Ferric Ions Influence On Synaptic Activity In Piriform Cmentioning

confidence: 99%

See 1 more Smart Citation

Effects of the blood components on the AMPA and NMDA synaptic responses in brain slices in the onset of hemorrhagic stroke

Mokrushin¹,

Pavlinova²

2013

gpb

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“…The neurological functional deficits after ICH are caused by damage to both gray matter (neurons and astrocytes) and white matter (axons and myelin-producing oligodendrocytes) [2] [3]. Injured oligodendrocytes do not form new myelin sheaths and mature oligodendrocytes do not proliferate in the adult brain [4].…”

Section: Introductionmentioning

confidence: 99%

Thymosin <i>β</i>4 Improves Neurological Outcome and Enhances Induced Oligodendrogenesis in the Rat after ICH

Yang¹,

Han²,

Chopp³

et al. 2014

WJNS

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Thymosin β4 (Tβ4), a G-actin binding protein, has diverse biological functions. This study tested the effects of Tβ4 on oligodendrogenesis in a rat model of intracerebral hemorrhage (ICH). ICH was induced by stereotactic injection of 100 µm of autologous blood into the striatum in 32 male Wistar rats. The rats were randomly divided into four groups: 1) saline control group (n = 8); 2) 3 mg/kg Tβ4-treated group (n = 8); 3) 6 mg/kg Tβ4-treated group (n = 8); and 4) 12 mg/kg Tβ4-treated group (n = 8). Tβ4 or saline was administered intraperitoneally starting at 24 h post ICH and then every 3 days for 4 additional doses. The neurological functional outcome was evaluated by behavioral tests (i.e., modified Neurological Severity Score and corner turn test) at multiple time points after ICH. Animals were sacrificed at 28 days post ICH, and histological studies were completed. Tβ4 treatment improved neurological functional recovery significantly and increased actively proliferating oligodendrocytic progenitor cells and myelinating oligodendrocytes in the ICH-affected brain tissue, compared with the saline-treated group. The high-dose treatment of Tβ4 showed better restorative effects compared with the low-dose treatment. Tβ4 treatment enhanced ICH-induced oligodendrogenesis that may contribute to the enhanced functional recovery after ICH. Further investigation is warranted to determine the associated underlying mechanisms of Tβ4 treatment for ICH.

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“…Intracerebral hemorrhage volume is itself a key factor in brain tissue damage. 2 However, secondary brain injury related to hemorrhage is also important, 3,4 which is reflected by the edema surrounding the hematoma, and has been a critical therapeutic target for ICH.…”

Section: Introductionmentioning

confidence: 99%

Detrimental Effects of Leptin on Intracerebral Hemorrhage via the STAT3 Signal Pathway

Kim

Ryu

Choi

et al. 2013

J Cereb Blood Flow Metab

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Leptin, one of the most important adipokines, is not only an energy regulator but also a regulator of innate immunity. Inflammation plays a key role in the tissue damage after intracerebral hemorrhage (ICH), and we sought to investigate whether leptin has a detrimental effect on ICH. After the injection of a high replacement dose (0.04 mg/kg) and two pharmacologic doses (4 and 8 mg/kg) of leptin, brain water contents increased significantly compared with that of control mice (Po0.05), which was confirmed when comparing the results with leptin-deficient ob/ob and wild-type (WT) mice (78.8% ± 0.6% versus 79.7% ± 0.6%, Po0.05). The number of Ox6-positive microglia/macrophages was increased in the leptin-injected group and decreased in ob/ob compared with WT mice. Among the candidate signal transducers, an increase in signal transduction and activator of transcription 3 (STAT3) levels was found after leptin injection. When we administered NSC74859, a specific inhibitor of phosphorylated STAT3 (pSTAT3), the water content became normalized. Activity of pSTAT3 was found mainly in Ox6-positive microglia/macrophages, but not in either neurons or astrocytes. We demonstrate that leptin plays a critical role in the secondary brain injury around a hematoma and is a novel mediator of the inflammation. This detrimental effect of leptin on ICH is mediated by the STAT3 signaling pathway in inflammatory cells.

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Intracranial Hemorrhage: Mechanisms of Secondary Brain Injury

Cited by 105 publications

References 67 publications

Effects of the blood components on the AMPA and NMDA synaptic responses in brain slices in the onset of hemorrhagic stroke

Effects of the blood components on the AMPA and NMDA synaptic responses in brain slices in the onset of hemorrhagic stroke

Thymosin <i>β</i>4 Improves Neurological Outcome and Enhances Induced Oligodendrogenesis in the Rat after ICH

Detrimental Effects of Leptin on Intracerebral Hemorrhage via the STAT3 Signal Pathway

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Intracranial Hemorrhage: Mechanisms of Secondary Brain Injury

Cited by 105 publications

References 67 publications

Effects of the blood components on the AMPA and NMDA synaptic responses in brain slices in the onset of hemorrhagic stroke

Effects of the blood components on the AMPA and NMDA synaptic responses in brain slices in the onset of hemorrhagic stroke

Thymosin &lt;i&gt;β&lt;/i&gt;4 Improves Neurological Outcome and Enhances Induced Oligodendrogenesis in the Rat after ICH

Detrimental Effects of Leptin on Intracerebral Hemorrhage via the STAT3 Signal Pathway

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Thymosin <i>β</i>4 Improves Neurological Outcome and Enhances Induced Oligodendrogenesis in the Rat after ICH