Clusterin contributes to caspase-3–independent brain injury following neonatal hypoxia-ischemia

10.1038/85487 ◽  
2001 ◽  
Vol 7 (3) ◽  
pp. 338-343 ◽  
Author(s):  
Byung Hee Han ◽  
Ronald B. DeMattos ◽  
Laura L. Dugan ◽  
Jeong Sook Kim-Han ◽  
Robert P. Brendza ◽  
...  
2016 ◽  
Vol 38 (4) ◽  
pp. 251-263 ◽  
Author(s):  
Armin Yazdani ◽  
Zehra Khoja ◽  
Aaron Johnstone ◽  
Laura Dale ◽  
Emmanouil Rampakakis ◽  
...  

Term asphyxiated newborns remain at risk of developing brain injury despite available neuropreventive therapies such as hypothermia. Neurorestorative treatments may be an alternative. This study investigated the effect of sildenafil on brain injury induced by neonatal hypoxia-ischemia (HI) at term-equivalent age. Neonatal HI was induced in male Long-Evans rat pups at postnatal day 10 (P10) by left common carotid ligation followed by a 2-hour exposure to 8% oxygen; sham-operated rat pups served as the control. Both groups were randomized to oral sildenafil or vehicle twice daily for 7 consecutive days. Gait analysis was performed on P27. At P30, the rats were sacrificed, and their brains were extracted. The surfaces of both hemispheres were measured on hematoxylin and eosin-stained brain sections. Mature neurons and endothelial cells were quantified near the infarct boundary zone using immunohistochemistry. HI caused significant gait impairment and a reduction in the size of the left hemisphere. Treatment with sildenafil led to an improvement in the neurological deficits as measured by gait analysis, as well as an improvement in the size of the left hemisphere. Sildenafil, especially at higher doses, also caused a significant increase in the number of neurons near the infarct boundary zone. In conclusion, sildenafil administered after neonatal HI may improve brain injury recovery by promoting neuronal populations.


2019 ◽  
Vol 20 (9) ◽  
pp. 2063
Author(s):  
Jia-Wei Min ◽  
Fan Bu ◽  
Li Qi ◽  
Yashasvee Munshi ◽  
Gab Seok Kim ◽  
...  

Neonatal hypoxia–ischemia (HI) is a major cause of death and disability in neonates. HI leads to a dramatic rise in intracellular calcium levels, which was originally thought to be detrimental to the brain. However, it has been increasingly recognized that this calcium signaling may also play an important protective role after injury by triggering endogenous neuroprotective pathways. Calcium/calmodulin-dependent protein kinase kinase β (CaMKK β) is a major kinase activated by elevated levels of intracellular calcium. Here we evaluated the functional role of CaMKK β in neonatal mice after HI in both acute and chronic survival experiments. Postnatal day ten wild-type (WT) and CaMKK β knockout (KO) mouse male pups were subjected to unilateral carotid artery ligation, followed by 40 min of hypoxia (10% O2 in N2). STO-609, a CaMKK inhibitor, was administered intraperitoneally to WT mice at 5 minutes after HI. TTC (2,3,5-triphenyltetrazolium chloride monohydrate) staining was used to assess infarct volume 24 h after HI. CaMKK β KO mice had larger infarct volume than WT mice and STO-609 increased the infarct volume in WT mice after HI. In chronic survival experiments, WT mice treated with STO-609 showed increased tissue loss in the ipsilateral hemisphere three weeks after HI. Furthermore, when compared with vehicle-treated mice, they showed poorer functional recovery during the three week survival period, as measured by the wire hang test and corner test. Loss of blood–brain barrier proteins, a reduction in survival protein (Bcl-2), and an increase in pro-apoptotic protein Bax were also seen after HI with CaMKK β inhibition. In conclusion, inhibition of CaMKK β exacerbated neonatal hypoxia–ischemia injury in mice. Our data suggests that enhancing CaMKK signaling could be a potential target for the treatment of hypoxic–ischemic brain injury.


2003 ◽  
Vol 95 (5) ◽  
pp. 2072-2080 ◽  
Author(s):  
John W. Calvert ◽  
Changman Zhou ◽  
Anil Nanda ◽  
John H. Zhang

We have previously demonstrated that a transient exposure to hyperbaric oxygen (HBO) attenuated the neuronal injury after neonatal hypoxia-ischemia. This study was undertaken to determine whether HBO offers this neuroprotection by reducing apoptosis in injured brain tissue. Seven-day-old rat pups were subjected to unilateral carotid artery ligation followed by 2 h of hypoxia (8% oxygen). Apoptotic cell death was examined in the injured cortex and hippocampus tissue. Caspase-3 expression and activity increased at 18 and 24 h after the hypoxia-ischemia insult. At 18-48 h, poly(ADP-ribose) polymerase (PARP) cleavage occurred, which reduced the band at 116 kDa and enhanced the band at 85 kDa. There was a time-dependent increase in the number of terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL)-positive cells. A single HBO treatment (100% oxygen, 3 ATA for 1 h) 1 h after hypoxia reduced the enhanced caspase-3 expression and activity, attenuated the PARP cleavage, and decreased the number of TUNEL-positive cells observed in the cortex and hippocampus. These results suggest that the neuroprotective effect of HBO is at least partially mediated by the reduction of apoptosis.


2008 ◽  
Vol 86 (5) ◽  
pp. 1115-1124 ◽  
Author(s):  
Jayne M. Ness ◽  
Cary R. Harvey ◽  
Jason D. Washington ◽  
Kevin A. Roth ◽  
Steven L. Carroll ◽  
...  

2000 ◽  
Vol 276 (13) ◽  
pp. 10191-10198 ◽  
Author(s):  
Klas Blomgren ◽  
Changlian Zhu ◽  
Xiaoyang Wang ◽  
Jan-Olof Karlsson ◽  
Anna-Lena Leverin ◽  
...  

2000 ◽  
Vol 7 (1) ◽  
pp. 38-53 ◽  
Author(s):  
Byung Hee Han ◽  
Anselm D'Costa ◽  
Stephen A. Back ◽  
Maia Parsadanian ◽  
Shilen Patel ◽  
...  

Oncotarget ◽  
2017 ◽  
Vol 8 (7) ◽  
pp. 12081-12092 ◽  
Author(s):  
Ana A. Baburamani ◽  
Kristina S. Sobotka ◽  
Regina Vontell ◽  
Carina Mallard ◽  
Veena G. Supramaniam ◽  
...  

Neuroreport ◽  
2000 ◽  
Vol 11 (13) ◽  
pp. 2833-2836 ◽  
Author(s):  
Malgorzata Puka-Sundvall ◽  
Ulrika Hallin ◽  
Changlian Zhu ◽  
Xiaoyang Wang ◽  
Jan-Olof Karlsson ◽  
...  

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