0:00

So moving on to term brain injury.

0:02

Uh, so the physiology here, so again, there's that primary,

0:05

secondary, tertiary insult,

0:06

but now it's kind of like directly related

0:08

to the delivery, right?

0:10

So before, right, the preterm, like some of

0:12

that stuff we couldn't control

0:13

because it might've been endogenous or, or the,

0:15

and the birth had to happen anyway.

0:17

Uh, but with the term, it's basically like you have some

0:19

kind of insult at the time of birth, around the time

0:22

of birth, the difficult delivery usually.

0:24

So we're, we're assuming that

0:25

that insult happened pretty much, you know, at that time.

0:28

So that initial insult could have been

0:29

hypoxic and or ischemic, right?

0:31

It could have been, um, the baby didn't get enough,

0:33

you know, good breaths.

0:34

Um, placental abruption, you know, the cord, uh,

0:39

ucoc cord, um, anemia, right?

0:43

Maternal or fetal, right? So lots of different etiologies,

0:46

placental, you know, thromboemboli.

0:49

Uh, but it's not just that primary insult, right?

0:51

The secondary energy failure.

0:53

So this initial insult actually induces a whole metabolic,

0:57

pro-inflammatory cascade,

0:59

and that causes additional injury on top

1:01

of the primary insult.

1:02

And the brain essentially fails to autoregulate, you know,

1:05

they're, they're newborns, right?

1:06

So they don't have the most mature cerebral autoregulation.

1:09

Um, and so in many times you can actually get a

1:12

rebound hyperperfusion.

1:13

So initially you've got low flow, right from

1:16

that initial HIE and then HII,

1:20

and then, um, the brain will respond

1:22

and maybe overcorrect, right?

1:23

And so basically more blood flow comes in,

1:25

but that actually leads to all this like free radicals

1:27

and apoptosis and all sorts of, uh, negative, uh,

1:31

negative kind of, um, feedback loops that, that lead

1:34

to essentially a lot more injury than

1:37

just the initial insult.

1:39

And then, uh, long term, right?

1:41

Months to years, you can have chronic ongoing injury from,

1:44

from this process.

1:45

So we wanna kind of blunt that.

1:47

And so the, the, the really only scientifically proven, um,

1:51

there are a number of adjuvants you can do, but,

1:54

but they don't necessarily provide added.

1:56

They may minimize, they may decrease hospital stay,

1:58

but the overall outcomes don't really change on, on top

2:02

of this therapeutic hypothermia.

2:03

So the idea is that there's this window

2:05

for the secondary energy failure over the first six hours

2:07

after the birth that you can actually blunt this response.

2:11

And how do you do that? You, you cool the baby down,

2:13

right from like 36, 37, you cool 'em down

2:16

to 33, 34 degrees Celsius for three, for three days.

2:19

And so you blunt that like hyperperfusion response, right?

2:23

So that you're not delivering the free radicals

2:25

and all this blood and inflammation to the RD damage brain.

2:28

So you minimize that, essentially

2:30

that secondary energy failure.

2:32

And then after that, you gradually rewarm them

2:34

back to normal temperature.

2:35

And so, because most MRI, uh, cooling, uh, sorry, uh,

2:39

most cooling systems are not MRI compatible.

2:41

This limits a lot of centers from doing the earlier imaging.

2:44

But as I said, right, you,

2:45

the immediate imaging is actually not as helpful as,

2:49

you know, like three to five days out.

2:50

So usually after rewarming and stabilization.

2:54

So, you know, around day four, if it's,

2:57

if you're really on the ball,

2:58

Or maybe five to seven, if, if it takes some time,

3:02

is when you see the majority of post cooling HIE pa uh,

3:06

infants at most centers.

3:07

And, um, that's, that's

3:09

what I think we're gonna show the most examples of.

3:12

So there's this little, um, uh, you know,

3:15

the vanilla ice I think was hot when I was growing up,

3:18

so I'm dating myself now, but he had a song, ice, ice baby.

3:21

But, uh, in, in the modern day, it probably is more useful

3:24

to re uh, to, to apply to this therapeutic hypothermia.

3:28

So basically they just wrap them in a, a blanket, right?

3:31

And they cool them and they pass the cooling fluid

3:33

constantly through their, their body and also their head.