Open AccessSpatio-temporal course of macrophage-like cell accumulation after experimental embolic stroke depending on treatment with tissue plasminogen activator and its combination with hyperbaric oxygenation
Author(s) -
Dominik Michalski,
Mario Heindl,
Johannes Kacza,
Félix Laignel,
Lea Küppers-Tiedt,
Dietmar Schneider,
Jens Grosche,
Johannes Boltze,
Mario Löhr,
Carsten Hobohm,
Wolfgang Härtig
Publication year - 2012
Publication title -
european journal of histochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.754
H-Index - 42
eISSN - 2038-8306
pISSN - 1121-760X
DOI - 10.4081/ejh.2012.14
Subject(s) - astrogliosis , microglia , tissue plasminogen activator , neun , neuroprotection , glial fibrillary acidic protein , medicine , inflammation , stroke (engine) , pathology , macrophage , astrocyte , gliosis , plasminogen activator , pharmacology , chemistry , central nervous system , immunohistochemistry , biochemistry , mechanical engineering , engineering , in vitro
Inflammation following ischaemic stroke attracts high priority in current research, particularly using human-like models and long-term observation periods considering translational aspects. The present study aimed on the spatio-temporal course of macrophage-like cell accumulation after experimental thromboembolic stroke and addressed microglial and astroglial reactions in the ischaemic border zone. Further, effects of tissue plasminogen activator (tPA) as currently best treatment for stroke and the potentially neuroprotective co-administration of hyperbaric oxygen (HBO) were investigated. Rats underwent middle cerebral artery occlusion and were assigned to control, tPA or tPA+HBO. Twenty-four hours, 7, 14 and 28 days were determined as observation time points. The accumulation of macrophage-like cells was semiquantitatively assessed by CD68 staining in the ischaemic area and ischaemic border zone, and linked to the clinical course. CD11b, ionized calcium binding adaptor molecule 1 (Iba), glial fibrillary acidic protein (GFAP) and Neuronal Nuclei (NeuN) were applied to reveal delayed glial and neuronal alterations. In all groups, the accumulation of macrophage-like cells increased distinctly from 24 hours to 7 days post ischaemia. tPA+HBO tended to decrease macrophage-like cell accumulation at day 14 and 28. Overall, a trend towards an association of increased accumulation and pronounced reduction of the neurological deficit was found. Concerning delayed inflammatory reactions, an activation of microglia and astrocytes with co-occurring neuronal loss was observed on day 28. Thereby, astrogliosis was found circularly in contrast to microglial activation directly in the ischaemic area. This study supports previous data on long-lasting inflammatory processes following experimental stroke, and additionally provides region-specific details on glial reactions. The tendency towards a decreasing macrophage-like cell accumulation after tPA+HBO needs to be discussed critically since neuroprotective properties were recently ascribed to long-term inflammatory processes