Inspired by Giaja

Stroke treatment

Conference in New York (2008)

In spring of 2008 Prof. Pavle R. Andjus, N.Y. Acad. Sci. Member, received information on a NYAS conference on Hypothermia as a treatment paradigm in acute stroke. Writing to the organizers that he would be delighted to take part and present the pioneering works of Prof. Giaja he also asked if the name, also appearing in Nature, was familiar to them. The organizers responded that they did not know of Giaja but would be glad to hear and offered Prof. P.R. Andjus to present the work of Giaja’s School during discussion session. Unfortunately, Prof. Andjus could not find sponsors for such a trip and never appeared at the meeting in New York. The field continued to develop without the groundbreaking knowledge of Giaja’s School…


 

Maintenance of functional cord blood CD34+ hematopoietic stem and progenitor cells

Applying analogy with Djaja’s “resuscitated” animals, the atmosphere of hypoxia and hypercapnia allowed to introduce the stem cells in the hypometabolic state, which, consequently resulted in their long-term survival at temperatures approaching zero enabling their conservation without a classical cryopreservation (freezing). … Similar results were obtained with the cells of different ontogenic and evolutionary origin, suggesting that the mechanism of cell introducing in hibernation-like state is rather universal.

Marija Vlaški & Zoran Ivanović
Etablissement Français du Sang Aquitaine-Limousin, Bordeaux, France

You can read the full text here.


 

Morphological changes in the hippocampus after hypothermia in both a hibernating and a non-hibernating animal

A study was made at electron microscope level of changes in the three-dimensional (3-D) morphology of dendritic spines and postsynaptic densities (PSDs) in CA1 of the hippocampus in ground squirrels, taken either at low temperature during hibernation (brain temperature 2–4 °C), or after warming and recovery to the normothermic state (34 °C). In addition, the morphology of PSDs and spines was measured in a non-hibernating mammal, rat, subjected to cooling at 2 °C at which time core rectal temperature was 15 °C, and then after warming to normothermic conditions. Significant differences were found in the proportion of thin and stubby spines, and shaft synapses in CA1 for rats and ground squirrels for normothermia compared with cooling or hibernation. Hypothermia induced a decrease in the proportion of thin spines, and an increase in stubby and shaft spines, but no change in the proportion of mushroom spines. The changes in redistribution of these three categories of spines in ground squirrel are more prominent than in rat. There were no significant differences in synapse density determined for ground squirrels or rats at normal compared with low temperature. Measurement of spine and PSD volume (for mushroom and thin spines) also showed no significant differences between the two functional states in either rats or ground squirrels, nor were there any differences in distances between neighboring synapses. Spinules on dendritic shafts were notable qualitatively during hibernation, but absent in normothermia. These data show that hypothermia results in morphological changes which are essentially similar in both a
hibernating and a non-hibernating animal.

This publication cites work of R.K. Andjus:

  • R.K. Andjus, A.U. Smith. Reanimation of adult rats from body temperatures between 0 and +20° C. J Physiol, I28 (1955), pp. 446–472 [link]
  • R.K. Andjus, F. Knöpfelmacher, R.W. Russel, A.U. Smith. Effects of hypothermia on behaviour. Nature, 176 (1955), pp. 1015–1016 [link]

Typical representatives of thin and mushroom spines and their PSDs (red) in stratum radiatum of CA1 hippocampal area of (A) ground squirrels, and (B) rats. All 3-D reconstructions are at the same magnification. For comparison of size, a cube with a side of 1 μm is shown in Figure A. Dendritic spines from ground squirrel (A) are considerably larger than in rats (B).

A summer story from MBL Woods Hole, USA

After talking to a longtime collaborator of prof. R.K. Andjus, Dr. Tasa Ćirković, neurophysiologist Dr. Dejan Zečević (Yale University) and Dr. Maja Djurišić,  a young post-doc both descendants of the Giaja School, discovered an interesting phenomenon. In a trial experiment they used Giaja’s hypercapnic chamber to cool a rat to body temperature 15°C. After such “cold anesthesia” brain slices isolated from these animals were much healthier as compared to rats with standard anesthesia. Dejan could not implement this technique back in his home lab since the ethics committee did not approve due to animal suffering during suffocation…