PMID- 38485848
OWN - NLM
STAT- MEDLINE
DCOM- 20240318
LR  - 20240318
IS  - 0942-0940 (Electronic)
IS  - 0001-6268 (Print)
IS  - 0001-6268 (Linking)
VI  - 166
IP  - 1
DP  - 2024 Mar 15
TI  - Pretreatment with a dual antiplatelet and anticoagulant (APAC) reduces 
      ischemia-reperfusion injury in a mouse model of temporary middle cerebral artery 
      occlusion-implications for neurovascular procedures.
PG  - 137
LID - 10.1007/s00701-024-06017-x [doi]
LID - 137
AB  - BACKGROUND: Several neurovascular procedures require temporary occlusion of 
      cerebral arteries, leading to ischemia of unpredictable length, occasionally 
      causing brain infarction. Experimental models of cerebral ischemia-reperfusion 
      injury have established that platelet adhesion and coagulation play detrimental 
      roles in reperfusion injury following transient cerebral ischemia. Therefore, in 
      a model of cerebral ischemia-reperfusion injury (IRI), we investigated the 
      therapeutic potential of a dual antiplatelet and anticoagulant (APAC) heparin 
      proteoglycan mimetic which is able to bind to vascular injury sites. METHODS: 
      Brain ischemia was induced in mice by transient occlusion of the right middle 
      cerebral artery for 60 min. APAC, unfractionated heparin (UFH) (both at heparin 
      equivalent doses of 0.5 mg/kg), or vehicle was intravenously administered 10 min 
      before or 60 min after the start of ischemia. At 24 h later, mice were scored for 
      their neurological and motor behavior, and brain damage was quantified. RESULTS: 
      Both APAC and UFH administered before the onset of ischemia reduced brain injury. 
      APAC and UFH pretreated mice had better neurological and motor functions 
      (p < 0.05 and p < 0.01, respectively) and had significantly reduced cerebral 
      infarct sizes (p < 0.01 and p < 0.001, respectively) at 24 h after transient 
      occlusion compared with vehicle-treated mice. Importantly, no macroscopic 
      bleeding complications were observed in either APAC- or UFH-treated animals. 
      However, when APAC or UFH was administered 60 min after the start of ischemia, 
      the therapeutic effect was lost, but without hemorrhaging either. CONCLUSIONS: 
      Pretreatment with APAC or UFH was safe and effective in reducing brain injury in 
      a model of cerebral ischemia induced by transient middle cerebral artery 
      occlusion. Further studies on the use of APAC to limit ischemic injury during 
      temporary occlusion in neurovascular procedures are indicated.
CI  - (c) 2024. The Author(s).
FAU - Denorme, Frederik
AU  - Denorme F
AD  - Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, 
      Belgium.
FAU - Frosen, Juhana
AU  - Frosen J
AD  - Hemorrhagic Brain Pathology Research Group, Dept. of Neurosurgery, Kuopio 
      University Hospital, Kuopio, Finland.
AD  - Department of Neurosurgery, Tampere University Hospital, Tampere, Finland.
FAU - Jouppila, Annukka
AU  - Jouppila A
AD  - Helsinki University Central Hospital Clinical Research Institute, Helsinki, 
      Finland.
FAU - Lindgren, Antti
AU  - Lindgren A
AD  - Department of Clinical Radiology, Kuopio University Hospital, Kuopio, Finland.
AD  - Institute of Clinical Medicine, School of Medicine, Faculty of Health Sciences, 
      University of Eastern Finland, Kuopio, Finland.
FAU - Resendiz-Nieves, Julio C
AU  - Resendiz-Nieves JC
AD  - Department of Neurosurgery, University of Helsinki and Helsinki University 
      Hospital, Helsinki, Finland.
FAU - Manninen, Hannu
AU  - Manninen H
AD  - Department of Radiology, Kuopio University Hospital, Kuopio, Finland.
FAU - De Meyer, Simon F
AU  - De Meyer SF
AD  - Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, 
      Belgium.
FAU - Lassila, Riitta
AU  - Lassila R
AUID- ORCID: 0000-0002-1911-3094
AD  - Coagulation Disorders Unit, Departments of Hematology and Cancer Center, Helsinki 
      University Hospital, Helsinki, Finland. riitta.lassila@kolumbus.fi.
AD  - Faculty of Medicine, Research Program in Systems Oncology, University of 
      Helsinki, Helsinki, Finland. riitta.lassila@kolumbus.fi.
AD  - Aplagon Oy, Helsinki, Finland. riitta.lassila@kolumbus.fi.
LA  - eng
PT  - Journal Article
DEP - 20240315
PL  - Austria
TA  - Acta Neurochir (Wien)
JT  - Acta neurochirurgica
JID - 0151000
RN  - 0 (Anticoagulants)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Anticoagulants/pharmacology/therapeutic use
MH  - Infarction, Middle Cerebral Artery/drug therapy
MH  - Brain/metabolism
MH  - Heparin/pharmacology/therapeutic use
MH  - *Brain Ischemia/drug therapy/metabolism
MH  - *Reperfusion Injury/drug therapy
MH  - *Brain Injuries
PMC - PMC10940479
OTO - NOTNLM
OT  - APAC
OT  - Anticoagulant
OT  - Antiplatelet
OT  - Cerebral ischemia
OT  - Infarct
OT  - Ischemia-reperfusion injury
OT  - Transient
COIS- RL is the Chief Scientific and Medical Officer of Aplagon Ltd. All other authors 
      declare no conflict of interest.
EDAT- 2024/03/15 06:43
MHDA- 2024/03/18 06:43
PMCR- 2024/03/15
CRDT- 2024/03/15 00:22
PHST- 2023/12/05 00:00 [received]
PHST- 2024/02/14 00:00 [accepted]
PHST- 2024/03/18 06:43 [medline]
PHST- 2024/03/15 06:43 [pubmed]
PHST- 2024/03/15 00:22 [entrez]
PHST- 2024/03/15 00:00 [pmc-release]
AID - 10.1007/s00701-024-06017-x [pii]
AID - 6017 [pii]
AID - 10.1007/s00701-024-06017-x [doi]
PST - epublish
SO  - Acta Neurochir (Wien). 2024 Mar 15;166(1):137. doi: 10.1007/s00701-024-06017-x.