Comparison of humoral neuroinflammation and adhesion molecule expression in two models of experimental intracerebral hemorrhage

We compared neuroinflammatory pathways in the two most common murine models: striatal injection of autologous blood or collagenase. Expression of pro- and anti-inflammatory cytokines (IL-1, TNF-α, IFN-γ, IL-6, TGF-β and IL-10) as well adhesion molecule expression (VCAM-1, ICAM-1) was analyzed by RT-PCR at several time points after ICH induction. Outcome and physiological parameters were compared between the models.Both models induced a profound and dynamic increase in the expression of pro-inflammatory cytokines and adhesion molecules. However, blood injection resulted in significantly more pronounced alteration of these markers than collagenase injection. This difference was associated with worse outcome after blood injection compared to the collagenase model despite equal ICH volumes.This is the first study performing a face-to-face comparison of neuroinflammatory pathways in the two most widely used murine ICH models, revealing substantial differences between the models. This discrepancies need to be taken into account in designing future studies employing experimental ICH models, especially when analyzing neuroinflammatory pathways and therapies.Intracerebral hemorrhage (ICH) represents about 10-15% of all strokes. Compared to ischemic stroke, it is associated with substantially higher morbidity and mortality [1,2]. In contrast to the major importance of ICH as a health care problem, no specific therapy for ICH is available until now. Moreover, the current understanding of crucial pathophysiological mechanisms is limited [3].To improve the search for potential therapeutic targets in ICH, several rodent models of ICH have been developed [4-6]. The most widely used techniques are direct injection of either blood or of collagenase, respectively [4,7,8]. Collagenase digests the extracellular matrix of small vessels and dose-dependently causes blood extravasation. Although both methods fail to reflect important components of the pathophysiology of ICH in patients [9]