Table 1.
Examples of conditioning paradigms in the developing brain.
| conditioning stimulus | pre-/ post-/ remote, +/− conditioning | severe insult | model | outcome/remarks | reference |
|---|---|---|---|---|---|
| 3 h of 8% hypoxia 24 h prior to insult | Pre + | 3 h of HI | 7-day-old rats | After 1 week no brain injury in pre-C group compared with 34% hemispheric loss in sham group. | Gidday et al., 1994 |
| 3 h of 8% hypoxia 24 h prior to insult | Pre + | 75 min of HI | 7-day-old rats | Performance in cylinder rearing test improved at 4, 6 & 8 weeks and In Morris water maze at 7 weeks in pre-C vs. sham; brain injury reduced by 72% in pre-C group. | Gustavsson et al., 2005 |
| LPS (TLR4 ligand) 0.3 mg/kg 2 h, 4 h, 6 h or 72 h prior to HI | Pre - | 10–50 min of HI | 7–10-day-old rats | LPS given 2 h, 4 h, 6 h or 72 h prior to 20–50 min of HI in 7-, 8- or 10-day-old rats significantly increased brain injury (vs. saline) at 3 days or 2 weeks after HI. | Eklind et al., 2001; 2015 |
| LPS 0.3 mg/kg 24 h prior to HI | Pre + | 20 or 50 min of HI | 8-day-old rats | LPS administered 24 h prior to 50 min (but not 20 min) of HI significantly reduced brain injury overall and In hippocampus, striatum and cortex 2 weeks after HI. | Eklind et al., 2015 |
| PAM3CSK4 (TLR2 ligand) 5 mg/kg 14 h prior to HI | Pre - | 50 min of HI | 9-day-old mice | PAM3CSK4 increased grey (by 14%) and white (by 13.7%) matter injury 5 days after insult. | Mottahedin et al., 2017 |
| Poly l:C(TLR3 agonist) 10 mg/kg 14 h prior to HI | Pre - | 50 min HI | 9-day-old mice | Poly l:C increased (vs. saline) infarction 5 fold, total tissue loss by 90% and white matter loss 5-fold 5 days after HI. | Stridh et al., 2013 |
| Limb ischemia (5 min, 3 times) immediately prior to HI | Remote, Pre + | 65 min HI | 14-day-old rats | Remote limb ischemia prior to HI reduced brain infarction by 71 % 7 days after HI. | Tropak et al., 2011 |
| Bilateral Limb ischemia (10 min, 4 times) immediately after HI | Remote, Post + | Cerebral HI adjusted depending on ATP peak measured by 31P MRS | 1-day-old (<30 h) piglets (model of HIE) | Limb ischemia reduced the Hi-Induced increase in white matter proton MRS lactate/N-acetyl aspartate and increased whole brain 31P MRS ATP over 48 h after HI. Cell death and Inflammation were reduced in several brain areas at 48 h. | Ezzati et al., 2016 |
| Hypoxia (8% 02 for 1 h/day for 5 d) 24 h after HI | Post + | 3 h HI | 7-day-old rats | Delayed hypoxic post-C reduced tissue loss, IL-10, astroglia and microglia activation 7 days after HI. | Teo et al., 2015 |
| Dexamethasone (0.1 mg/kg) 24 h prior to Hi | Pre + | 3 h HI | 7-day-old rats | A single dose of dexamethasone 24 h (but not 3 h or 0 h) prior to HI prevented the development of brain injury 7 days after HI. | Barks et al., 1991 |
| Xenon (2 h of 70% xenon/30% 02) 4ߝ24 h prior to HI | Pre + | 2 h HI | 7-day-old rats | Xenon applied 4 h, 8 h or 24 h (but not 2 h)priorto HI substantially reduced brain injury 4 days after HI and motor and neurological coordination at 30 days. | Ma et al., 2006 |
| MgS04 (1.1 mg/g) 12 h-6 days prior to HI | Pre + | 1 h HI | 7-day-old rats | MgS04 reduced brain injury In white and grey matter when given 12 h-6 days prior to HI but not 0 n, 3 h before or after HI. Brain injury was reduced by >80% when MgS04 was given 24 h prior to Insult. ‘ | Koning et al., 2017 |
Abbreviations: Hypoxia-ischemia (HI); hypoxic-ischemic encephalopathy (HIE); lipopolysaccharide (LPS); magnetic resonance spectroscopy (MRS); magnesium sulphate (MgSO4); negative conditioning (−); polyinosinic: polycytidylic acid (poly I:C); positive conditioning (+).