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. ADOCKE T —A-N—UtTRA'STRUCTURA L STUDY O P TH E EFFECT S O F LEA D I NTH E

CENTRA L NERVOU S SYSTE M O F TH E RAT . H . Reyners , S.Gianfelic i d e Reyner s and J.R.Maisi n ABSTRAC T t

Th e glia l balanc e i s highl ysensitiv e t o lea d intoxication , a t leas t i n 3 mont hol d femal e rats , wher e dose s a s lowa s 10 0 ppm P bgive n i n foo d ( frombit h) ca n caus e a n increasei n densit yo f astrocyte s and microgli a compensate d b ya reductio n o f oligodendrocytes . INTRODUCTIO Nt Lea d i s a powerfu l environmenta l toxi c an d it s delete
riou s actio n o n th e nerv e matte r ha s ofte n bee n reported . Th e poisonou s * effec t ha s generall ybee n admitte d t o b e du e t o a specifi c injur yo n vascula r element s (re f 1) . Nevertheless , thi s ca n b e questione d becaus e o f th e ver yhig htoxi e level s assaye d i n curren t neuropathologica l re searc h(ref s 2 & 3) . Indeed , w e hav e recentl ynote d tha t relativel y mil d dose s ca n eve n produc e hypervascularizatio n i n th e cerebra l cor te xo f th e ra t possibl yi n relatio n wit ha sever e involutio n o f th e neuropil e (re f 4) . I n th e presen t work , significan t quantitativ e par enchyma l modification s ar e reveale d afte r ver ylo wleve l lead poisoning . MATERIA L & METHOD S : Experimenta l lead encephalopath yi s produce d i n rat s b ymean s o f th e Pentsche w& Garr o mode l (re f 1 ) bu t wit hth e us e o f lowe r lead levels . Capillar yand glia l densitie s ar e evaluate d i n ra t brain s b

ymorphometri c method s (ref s 4 & 5) « RESULT S & DISCUSSIO N: Capillar ydensit yalthoug hincrease d i n mil d intoxicatio n ( 1000 0 ppmP bi n foo d ) doe s no t reac hth e contro l leve l i n 10 0 ppmlead treate d rats . Thes e variation s appea r correlate d t o th e corte xthicknes s change s ( fi g 1 ) . Indeed , th e produc t o f ca pillar ydensit yb

ycorte xthicknes s remain s constan t i n th e use d dos e rang e ; thi s indicate s tha t th e absolut e numbe r o f cortica l capillarie s i s no t modifie d b

ylead . Th e change s i n corte xparenchym e wer e thu s considere d a s th e independen t variabl e o f th e system . I n thi s paper , ou r interes t i s the n focuse d o n glia l cell s whic happeare d t o b e muc h mor e sensitiv e tha n previousl ysuppose d (re f 6) , althoug hi n a se x 

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p^~4 . ~ ^ J iP-i.. . J ^ „ tT.. A uc^; w , » ^ p wGnv ^ T ^ -» J ^ n..iiin Am mP. 3 

## 5 9

TABL E I Pb + + dos e i n ppm

10 0

100 0

500 0

1000 0 Femal e Mal e

Glia l typ e 

### A 0 M TOT : 

### A 0 M TOT : 

### A 0 M TOT : 

### A 0 U TOT : 

### A 0 M TOT : 

### C 49 5 39 3 10 9 99 7 44 9 37 4 10 7 930n s 

### 53 3 33 9 12 5 997 s 

### 58 0 34 4 21 7 

### S 9 1 9 2 4 4
7 4 

### 10 3 3 7
7 8 8 4 5 8
8 4 9 7 

### 11 5 1141SS S 

### 45 0 26 8 21 5 7 4 6 3 

### 10 1 933SSSB S +

+ + +

4 + +

4 4 +

+

- t +

+ 4 4 

### NS 

### 40 4 30 1 6 5


### 37 5 27 1 7 0


### 45 5 25 5 6 7


### 49 6 24 7 10 2 37 6 20 5 11 4 

## £ s 18. 4 23. 4 40. 4
16.5n s 27.5n s 34.6n s
14.6n s 24.8n s 46.4n s
14.5s ? 28.2n s 53.0 s
16.4n s 23.5n s 47. 0 n s 

### C

48 1 28 1 11 8 88 0 46 9 30 1 11 4 884n s 

### 42 5 34 0 11 3 878s s 

### 54 5 34 5 19 0 1080 s 

### S 6 5 7 3 5 6
7 2 7 6 6 0
5 7 

### '96 4 5
8 7 8 4 9 0 + 4 4 4

4 4 4

4 4 4

4 4 4 

### NS 

### 41 6 20 8 6 2


### 39 7 22 5 5 4 

### 36 8 24 4 6 8


### 45 8 26 1 10 0 

## * s 13. 5 26. 0 47. 5
15-4n s 25.3n s 52.6n s
13.4n s 28.2n s 39.8n s

• 6.0n s 24.4n s 47.4n s ;• !

Tabl e I : Effect s o f Lea d an d Se x '^

n th e Glia l Balanc e i n th e ra t a t 3 mont hold . Th e tota l o f glia l cell s ( TOT : ) i s subdivide d int o it s 3 component s : astrocyte s (A) , oligodendrocyte s (0 ) and micro
gli a (K) . Fo r eac ho f thes e cel l population s (C) , satellit e (S ) an d n o satellit e cell s ar e counte d an d th e percentag e o f satellitis m estatlished . Th e significanc e o f th e desequilibrium s betwee n contro l an d treate d population s i s estimate d throug ha 2-wa yG test . dependen t way . AG-tes t analysi s o f th e glia l balanc e betwee n astro cytes , oligodendrocyte s and microgli a i s abl e t o revea l significan t change s (tabl e I ) i n thei r equilibrium . Th e olig o behaviou r i s sex linke d : thes e cell s appea r t o b e muc hmor e sensitiv e i n femal e rats , a fac t whic hca n b e correlate d t o th e ofte n reporte d majo r lead sen sitivit yo f femal e individuals . Satellitis mfo r nerv e cell s i s als o quantitativel yevaluate d bu t i s no t found verymodifie d a s i n th e cas e o f x-irradiate d brain s ( Reyner s e t al. , i n prep.) .6 0

2 -

1 - corte xthickness ,

(mm )


## <t >-^ — 

# r

$9 capillarydensity
. (nVmm* ) 

# C 

# ^^\ 4 * ~ " ^J ^ ^

**0.tSS* S '"" • probability

ot eurvn: br two *mr MOM . of pointt: by t Int. •P > 0.J 5 • •P ; ai t dos e P&* T'SO O

25 0



### 1 0 10 0 

### 100 0 1000 0 pp m Fi g 1 : The variation s o f capillar y densit y

i nlea

dtreatedcortex ar e correlate dt o th e change s i nth

e cortexthickness .

300 - f

20U +

100 + 

### Glia l densit y (n'/mm* )

Microglia
. C O 

### dos e Pb " 10 too 1000 10000 PP m Fi g 2 I Evolutio no f th e glia l population s i nth e cerebra l cortex o f rat s intoxicatedwit hvariou s dose s o f lea dacetat e an dobservedat 3 mont hold . The effec t o f treatmen t i sP. 5



### 6 1
I n conclusion , the presen t repor t show s tha t vascula r element s ar e no t the majo r an

d onlyfacto r a t ris k i n experimenta l lea d encepha
lopathy . Moreover , the significan t glia l populatio n change s reveale d her e a t dose s whic hdo no t promot e an yvisibl e vascular troubl e pin
poin t the glia l nerve suppl ya s a rea l targe t o f heav ymetal s an

d consequentl ya s a sourc e o f potentia l damag e t o brai n functio n ( re f 7) . REFERENCE S 1 . APentschewan

d F Garro , Act a Neuropat h£,26 6 (1966 ) 2 . R AClasen , J F Hartman , J AStarr , P S Coogan , S Pandolfi , I Laing , R Becke r an

d G M Hass , A

mJ Pat h74. , 21 5 (1974 ) 3 . A D Toews , AKolber , J Hayward , M R Krigman an d P Morell , Brai n Re s 147 , 13 1 (1978 ) 4 . H Reyners , E Gianfelic i de Reyner s an d J R Maisin , Experienti a 32. , 141 6 (1976 ) 5 . D W Vaughan an

d APeters , J Neurocyto l 3_ , 40 5 (1974 ) 6 . D V Marko van

d R NDimova , Act a Neuropat h_2j3 , 2 5 (1974 ) 7 . G Winneke , ABrockhau s an d R Baltissen , Arc hToxico l ^7. , 24 7 (1977 )P. 6 

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