• Log in with Facebook Log in with Twitter Log In with Google      Sign In    
  • Create Account
  LongeCity
              Advocacy & Research for Unlimited Lifespans

Photo
- - - - -

NMN vs. Clot-Buster Bleeds

nmn nicotinamide mononucleotide stroke nad

  • This topic is locked This topic is locked
1 reply to this topic
⌛⇒ new years donation: support LE labs

#1 Michael

  • Advisor, Moderator
  • 1,254 posts
  • 1,730
  • Location:Location Location

Posted 17 August 2017 - 05:33 PM


All:

 

There's been previous evidence that nicotinamide is neuroprotective in stroke models, acting as an NAD precursor and preventing excitotoxic cell death by overconsumption of NAD by PARP1 and SIRT1.

 

The clotbuster  recombinant tssue plasminogen activatora (rtPA, alteplase) is an important rescue drug in ischaemic stroke, breaking up the clot and restoring blood and oxygen flow, preventing further neuronal destruction. However, sometimes — particularly if it is delivered late in the game (>5 hours after a stroke), rtPA can greatly increase the risk of a secondary bleed into the affected zone of the brain— a process called haemorrhagic transformation (HT). Estimates vary, but 10-40% of patients with ischemic (oxygen-starvation, usually clot-driven) stroke leads to HT, which is associated with increased morbidity and mortality after a stroke.

 

This rather artificial rodent study found that 300 mg/kg, but not 100 mg/kg, of NMN reduced the severity of HT resulting from rtPA administration 5 hours after a simulated stroke.

 

 

Middle cerebral artery occlusion (MCAO) was achieved in CD1 mice by introducing a filament to the left MCA for 5 hours. When the filament was removed for reperfusion, tPA was infused from tail vein. NMN was injected intraperitoneally with a single dose (300 mg/kg [or 100 mg]). ...

KEY RESULTS:

In the mice infused with tPA at 5 hours post ischemia, there were significant increases in mortality, brain infarction, brain edema, brain hemoglobin level, neural apoptosis, Iba-1 staining ([inflammatory] microglia activation) and MPO staining (neutrophil infiltration). All these tPA-induced alterations were significantly prevented [it would be more accurate to say "reduced"] by NMN administration [at 300 mg/kg but not 100 mg/kg]. Mechanistically, the delayed tPA treatment induced [blood-brain barrier (BBB)] permeability by downregulating tight junction proteins, including claudin-1, occludin and ZO-1, and enhancing the activities and protein expression of [matrix metalloproteinases] MMP9 and MMP2. Similarly, NMN administration partly blocked these tPA-induced molecular changes.


  • like x 2
  • Good Point x 1

#2 Benko

  • Guest
  • 213 posts
  • 325
  • Location:US

Posted 23 August 2017 - 12:38 PM

Thanks for posting this--this is a big deal.







Also tagged with one or more of these keywords: nmn, nicotinamide mononucleotide, stroke, nad

0 user(s) are reading this topic

0 members, 0 guests, 0 anonymous users